• mitochondria
• peroxisomes
• endoplasmic reticulum 
• lysosomes
• golgi apparatus

• cytoskeleton
• centrioles
• ribosomes 

• most cells are uninucleate
• RBCs are anucleate
• skeletal muscle cells, bone destruction cells, & some liver cells are multinucleate

• separates intracellular fluid (ICF) from extracellular fluid (ECF)
• maintains cell structure 
• chemical & physical barrier (impermeable)
• allows cell communication
• regulates water & solute exchange (semipermeable) 

• lipid bilayer or leaflets, amphipathic, impermeable to charged, large, & water soluble molecules
• phophate heads - polar & hydrophilic
• fatty acid tails - nonpolar & hydrophobic 

• adhesion molecules
• transport proteins
• enzymes 
• receptors
• intracellular signaling 

• ionic interactions
• subcortical cytoskeleton
• motor proteins
• cell-to-cell links
• support on intracellular surface, part of glycocalyx 

• plasma membranes are selectively permeable
• phospholipid bilayer is impermeable to charged & water-soluble molecules

• passive processes (pass down a concentration gradient)
• active processes (ATP)

• lipid solubility of substance
• molecular size
• composition of lipid bilayer
• cell membrane thickness
• concentration gradient
• membrane surface area
• electrical charge

Fick's Law of Diffusion says what?

rate of diffusion = [(available surface area) x (conc. gradient)]

                            ___________________________________

               [(membrane resistance) x (thickness of membrane)]

membrane resistance = lipid solubility / molecular size

changing the composition of the lipid layer can inc or dec membrane resistance 

• porins: in outer membranes of mitochondria 
• perforin: released by lymphocytes, allows passive flow of ions, water, small molecules
• aquaporin: single-file diffusion of water
• nuclear pore complex

• ungated/leakage channels: always open; determined by size, shape, distribution of charge, etc. 
• gated channels: controlled by chemical or electrical signals (such as voltage dependent Na+ channels or nicotinic ACh receptor channels) 

binding of a substrate causes shape change in carrier

• two gates that are never open at the same time
• specific affinity for binding one or a small # of solutes (so only binds to specific molecules)
• ex: glucose transporter GLUT which is important in diabetes

• active transport
• vesicular transport

both use energy (ATP) to move solutes across living plasma membrane 

• requires carrier proteins (solute pumps)
• moves solutes against concentration gradient
• two types: primary act. trans. & secondary act. trans. 

• energy from hydrolysis of ATP causes shape change in transport protein
• sodium-potassium pump (Na⁺/K⁺ ATPase)

Describe the purpose of the Sodium-Potassium Pump 

(Na⁺/K⁺ ATPase) in all plasma membranes:

• primary & secondary active transport of nutrients & ions
• maintains electrochemical gradients essential for functions of muscle & nerve tissues 
• α subunit binds ATP, 3 Na⁺, & 2 K⁺; also β subunit
• transport is electrogenic but contributes >10% membrane potential 

What is the purpose of the Ca²⁺ ATPase Pump?

• important in muscle contraction
• cell membrane & sarcoplasmic reticulum
• maintains low cytosolic Ca²⁺ concentration 

What is the purpose of the H⁺ ATPase Pump?

• important in stomach secretion & kidney regulation of blood pH
• parietal cells of gastric glands (HCl secretion) & intercalated cells of renal tubules (controls blood pH)
• concentrates H⁺ ions up to 1 million-fold

• cytoplasmic Na⁺ binds to pump protein
• binding of Na promotes phosphorylation of protein by ATP
• phosphorylation causes protein to change shape, expelling Na⁺ to outside
• extracellular K⁺ binds to pump protein 
• K⁺ binding triggers release of phosphate; pump protein returns to original conformation 
• K+ released from pump protein & Na⁺ sites read to bind Na⁺ again (*repeat cycle*)

always transports more than one substance at a time

• symport system - 2 same direction
• antiport system - 2 opp. direction

As Na⁺ diffuses back across the membrane through a membrane cotransporter protein, it drives what

against its concentration gradient into the cell.

inhibit Na⁺/K⁺ ATPase

(for ex: digoxin is the cornerstone for treatment of heart failure) 

• inc. intracellular Na⁺
• dec. Na⁺ gradient
• dec. Na⁺/Ca²⁺ counter-transport
• inc. intracellular Ca²⁺
• alters secondary active transport mechanism inside the cell; if there is no Na⁺ gradient, then Ca²⁺ cannot be moved

• transport of large particles, macromolecules, & fluids across plasma membranes 
• requires cellular energy (ATP and calcium) 

• endocytosis: transport into cell
• transcytosis: transport into, across, & out of cell (from molecule that came from outside of cell)
• exocytosis: transport out of cell
• trafficking: transport from one area or organelle in cell to another (comes from inside cell)

• Phagocytosis
• receptor-mediated endocytosis
• pinocytosis

• pseudopods engulf SOLIDS (phagosome) which is combined with a lysosome 
• undigested contents remain in vesicle (residual body) or are ejected by exocytosis
• ex: macrophages & some white blood cells

• Clathrin-coated pits
• uptake of ligands (enzymes, low-density lipoproteins, iron, & insulin)
• ligands may be released inside cell or combined w/ lysosome to digest contents
• receptors recycled to plasma membrane in vesicles 

• plasma membrane infolds, bringing extracellular FLUID and SOLUTES into interior of cell (common in digestion)
• ex: nutrient absorption in small intestine 

• hormone secretion
• neurotransmitter release
• mucus secretion
• ejection of wastes

1. membrane-bound vesicle migrates to the plasma membrane
2. proteins at vesicle surface (v-SNAREs) bind w/ t-SNAREs (plasma membrane proteins)
3. vesicle & plasma membrane fuse & pore opens up
4. vesicle contents are released to cell exterior 

The secretion of hormones and

neurotransmitters using ATP is an example of:

Diffusion:

• occurs DOWN conc. gradient; no mediator or involves "channel" or "carrier"
• no additional energy

The total body water is ______% of the total body weight.

What percentage is intracellular/extracellular? What is each environment rich in?

• 50-60% of total body weight
• 60% intracellular (rich in K⁺)
• 40% extracellular (rich in Na⁺ and Cl^-)

• interstitial fluid (75%): bathes non-blood cells
• blood plasma (20%): bathes blood cells
• transcellular fluid (5%): surrounded by epithelial cells, eg. synovial & cerebrospinal fluids

number of positive & negative charges must be equal; there is a difference b/n major cations & anions in blood plasma, defined as anion gap

• through the lipid bilayer
• through water channels called aquaporins (AQPs)

• if soln B is more concentrated than soln B & the 2 compartments are separated by a membrane that is permeable to water, but not glucose, water will move (by osmosis) into more concentrated soln B until conc. equal
• osmotic pressure is pressure that must be applied to soln B to oppose osmosis from A to B

• dominated by [Na⁺] and the associated anions
• Na⁺ 130-140mmol 
• P_OSM = 2 X (135‐145)= 270‐290 mOsm
• 150 mM NaCl = 300 mOsm (Saline or 0.9% NaCl)
• 300 mM glucose = 300 mOsm

Under normal conditions, ECF osmolarity can be roughly

estimated as:

P_OSM = 2 [Na⁺]_p                                   270‐290 mOSM

• Na⁺ 130-140mmol 
• P_OSM = 2 X (135‐145)= 270‐290 mOsm

• normal plasma osmolarity = 290 mOsm
• Isosmolar solutions = 290 mOsm
• Hyperosmolar solutions > 290 mOsm
• Hypo‐osmolar solutions < 290 mOsm

• Isotonic: A soln w/ the same solute conc. as that of the cytosol.
• Hypertonic: A soln having greater solute conc. than that of the cytosol.
• Hypotonic: A soln having lesser solute conc. than that of the cytosol.

• acute response: regulatory volume increase (RVI) by activating (1) Na⁺-H⁺ exchanger & Cl^-HCO^-₃ exchange or (2) Na⁺/K⁺/Cl^- cotransporter
• chronic response: accumulating intracellular organic solutes or transport them into the cytosol from the outside

• Decreases in [Na⁺] in the plasma and ECF (hyponatremia)
• Increases in [Na⁺] (hypernatremia)
• Increases in glucose concentration (hyperglycemia)

• will inc. ECF volume
• will have divergent effects on ICF volume & ECF osmolality

• this soln has effective osmolarity of 290 mOsm in ECF
• raises ecf volume w/o affecting ICF
• no change occurs in effective osmotic gradient across cell membrane
• added water moves neither into nor out of ICF

• inc. ECF & dilutes preexisting solutes in the ECF (lowering ECF osmolarity)
• large osmotic gradient created that favors entry of water from ECF into ICF

• inc osmolarity of ECF
• draws water out of ICF into ECF until osmotic equilibrium is re-established
• added ECF volume has come from ICF, then ICF shrinks

• barriers that separate ECF from outside world
• uninterrupted sheet of cells that are joined together by junctional complexes 

• the apical membrane, brush border, mucosal membrane, or luminal membrane
• the basolateral membrane, serosal, or peritubular membrane

• transcellular: by sequentially passing across the apical & then basolateral membranes (or vice versa)
• paracellular: bypassing the cell entirely & cross epithelium through tight junctions & lateral intercellular spaces 

voltage measured in resting state in all cells

• ranges from -50 to -100 mV in different cells (-90avg in cell body)
• results from diffusion & active transport of ions (mainly K⁺)

• Na⁺/K⁺ pump continuously ejects Na⁺ from cell & carries K⁺ back in. Some K⁺ continually diffuses down conc. gradient out of cell through K⁺ leakage channels.
• The immediate energy source of membrane potential is in ion concentration gradients.
• The ion pumps generate and maintain these ion gradients.

A steady state is maintained because the rate of active

transport is equal to and depends on the rate of Na+ diffusion

into cell.

Negative‐going V_m change

(normal is -90 so hyperpolarization would be -100)

Positive‐going change in V_m

(-50 would be more depolarized; more positive than normal)

• Connexins
• K⁺ Channels: largest family (Kv, SK_Ca and IK_Ca, BK_Ca…)
• Voltage‐Gated Channels/accessory proteins: Highly selective for Na⁺, Ca²⁺, or K⁺.
• Ligand‐Gated Channels: pentameric Cys‐loop, glutamate, Purinergic…
• Other Ion Channels: ENaC, CFTR, ITPR, RYR, ORAI storeoperated Ca²⁺ channels

• followed by a slower repolarizing (negative‐going) phase.
• Time course and shape vary among different excitable tissues and cells.

• electric signals cause a deviation in membrane potential of cell
• spread according to different mechanisms like electrotonic conduction (dendrites) & action potential (axons)

• All or none
• Constant amplitude
• Initiated by depolarization
• Involve changes in permeability
• Rely on voltage‐gated ion channels
• Constant conduction velocity. (Fibers w/ large diameter conduct faster than small fibers).

• info delivery to CNS
• info encoding
• rapid transmission over distance (nerve cell APs)

• block APs in sensory nerves by local anesthetics (analgesia w/o paralysis)
• blocking APs will block transmission of message but is dependent of what is being blocked (i.e. loss of pain feeling)

• the frequency of APs encodes info
• AMPLITUDE CANNOT CHANGE

• speed of transmission depends on fiber size & whether it is myelinated (myelination inc. speed)
• in non-nervous tissue: APs initiators of cellular responses like muscle contractions & secretion (like epinephrine from chromaffin cells of medulla)

The threshold, amplitude, time course, and duration of the

action potential depend on what factors?

• gating (opening/closing) & permeability prop. that depend on V_m & time
• IC & EC conc. of ions that pass through channels, like Na⁺, K⁺, Ca²⁺, & Cl^‐
• membrane prop. like capacitance, resistance, & geometry of cell.

Describe the mechanism of action potentials for the following situations:

• smaller or subthreshold depolarizations
• hyperpolarizations
• as V_m becomes progressively more positive

• smaller or subthreshold depolarizations: will not elicit an action potential
• hyperpolarizations: always ineffective
• as V_m becomes progressively more positive: the gating of certain types of voltage-gated ion channels becomes activated

• Magnitude of graded response decays exponentially w/ distance from site of stimulation due to loss of energy to medium.
• Passive spread of electrical potential; excitation of voltage-gated channels in adj. regions of excitable membrane regenerates response.
• Once Na⁺ channels opened & Na⁺ enters cell, membrane potential shifts toward Na⁺ equilibrium potential (positive)

chemical or electrical gradient

(potential dissipates as distance from source increases)

1. (Strength × Duration) of the Stimulus (minimum required)
2. Refractory Period.

• time that must elapse before it is possible to trigger a second action potential
• two phases of refractory period arise from gating properties of particular Na⁺ & K⁺ channels & overlapping time course of their currents

the time during which a second action potential cannot occur under any circumstances, aka Na+ channel inactivation.

(sodium channel MUST be open & activated for AP to occur)

• Neurotoxins (TTX and STX) altering the gating kinetics of Na⁺ channels (longer duration and under different voltage)
• Local Anesthetics (procaine, lidocaine, and tetracaine) by inhibiting voltage‐gated Na⁺ channels.

• contribute to action potentials in some cells
• function in electrical & chemical coupling mechanisms

• Depolarization phase of certain action potentials: basis for long‐lived APs observed in cardiac, smooth muscle, & secretory cells, & many types of neurons.
• Signal transduction processes.
• Excitation‐secretion coupling: (process by which depolarization of the plasma membrane causes release of NTs in the NS & the secretion of hormones in the endocrine system. (Such processes require inc. in Ca²⁺

• L-type (for long-lived)
• T-type (for transient) channels: activated @ lower voltage threshold

• used in treatment of cardiovascular disorders & potential in treatment of various diseases of CNS.
• 1,4‐dihydropyridines (DHPs), eg nitrendipine.
• Phenylalkylamines, (eg verapamil)
• Benzothiazepines (eg diltiazem)

• Determine resting potential
• Mediate termination of action potentials
• Control firing frequency and bursting behavior
• In epithelia, K+ absorption and secretion.

• Lengthening of the QT interval
• Congenital deafness (K⁺ channel important for ear processes)
• Premature heartbeats or asynchronous ventricular contraction, with subsequent death

Hydrophobic messengers (steroid hormones and some

vitamins) can diffuse across the plasma membrane and

interact with cytosolic or nuclear receptors.

• Gap junction (electrical and metabolic)
• Tight junction
• Adhering junction (Desmosome)

• Involves a receptor in the plasma membrane & a ligand that is a membrane protein on an adj. cell.
• E.g. ephrin in axonal and endothelial guidance

• Endocrine - distant target tissue
• Paracrine - same target tissue in neighboring cell, eg neuromuscular junction
• Autocrine - same cell that released the signal

• Amines (epinephrine)
• Peptides and Proteins (angiotensin II, insulin)
• Steroids (aldosterone, estrogens, retinoic acid)
• Small molecules (Aa, nucleotides, ions and gases)

• made of protein or lipoprotein
• on the cell (surface or inside; can be localized in any part of the cell)

• receptors specifically binds a signaling molecule (like an ion channel)
• ligand interaction w/ one or more receptors results in association of receptor w/ effector molecule (enzymes, channels transport proteins, contractile elements, & transcription factors)
• some molecules compete for receptors
• either direct or mediated effect; effect highly correlated to type of receptor

• the complement of receptor it possesses
• the chain of intracellular reactions that are initiated by the binding of any ligand to its receptor (signal transduction)

• membrane permeability
• metabolism
• secretory activity
• rate of proliferation and differentiation
• contractile activity

1. Ligand‐gated ion channels
2. Catalytic receptors
3. Nuclear receptors
4. G protein‐coupled receptors

Define Ligand‐gated ion channels:

• integral membrane proteins
• direct signaling b/n electrically excitable cells (eg. ACh)
• transduce a chemical signal into an electrical signal (ionotropic receptors)

• integral membrane proteins
• when activated by a ligand become enzymes or part of an enzymatic complex

• proteins in cytosol or nucleus
• ligand-activated transcription factors
• link extracellular signals to gene transcription

• integral membrane proteins
• indirect signaling, through an intermediary (G protein or GTP-binding complex) to activate/inactivate a separate membrane-associated enzyme or channel

1. recognition
2. transduction
3. transmission
4. modulation of the effector
5. response
6. termination

recognition of signal by its receptor that occurs by molecular interaction w/ receptor recognimtion of ligand

(ionic bonds, van der Waals & hydrophobic interactions)

Transduction of the extracellular message into an intracellular signal or second messenger.

• lipid-soluble molecules can bind straight to the transcription factor
• hydrophilic molecules must signal & bind to outside of the plasma membrane before taking effect 

1. catalytic activities intrinsic to the receptor
2. the receptor interacts with membrane or cytoplasmic enzymes (second messenger)

1. ligand (1st messenger) binds to receptor
2. activated receptor binds to G protein & activates it
3. activated G protein activates (or inactivates) effector protein (like enzyme) by causing its shape to change
4. activated effector enzymes catalyze rxns that produce 2nd messengers in cell
5. 2nd messengers activate other enzymes or ion channels
6. kinase enzymes transfer phosphate groups from ATP to specific proteins & activate a series of other enzymes that trigger various cell responses

• 1st: binding of the receptor leads to a direct cellular response
• 2nd: binding of a ligand to the receptor leads to another signaling event which eventually causes a cellular response

• Amplify signals & integrate responses among cell types
• Allows specificity & diversity
• Its concentration is regulated b/c of feedback mechanism
• There is cross‐talk among different signaling cascades

(ex: cAMP: receptor occupancy activates G protein, which

stimulates adenyl cyclase that catalyzes ATP to cAMP. cAMP

is broken down by cAMP phosphodiesterase)

Signal transduction systems that project to the cell

membrane or to the cytoplasm produce non‐genomic

effects

• Receptors for ACh
• Serotonin
• Gamma‐aminobutyric acid (GABA)
• Glycine
• IP₃ receptor
• Ca²⁺ release channel (ryanodine receptor)

• Guanylyl Cyclase (retina)
• Serine‐Threonine
• Tyrosine Kinase

• tranduces activity of ANP & raises intracellular levels of cCMP
• raising cGMP activates cGMP-dependent kinase (PKG or cGK) that phosphorylates proteins @ certain serine & threonine residues

• in cytosol
• transduces activity of nitric oxide
• as a result, cGMP inc & smooth muscles relax
• NO inc. diameter of vaculature & regulation of blood pressure

• Type II receptor first binds ligand & then type I receptor, which undergoes phosphorylation @ serine & threonine residues
• this activates kinase activity which propagates the signal to downstream effectors (Eg. TGF-beta)

(ligand+type II) > (type I) > (P-Type I) > (inc.kinase activity) > (downstream signaling) 

• phosphorylate themselves
• e.g. growth factors, EGF, PDGF, VEGF, insulin, IGF‐1, FGF, NGF bind to receptors with intrinsic Tyr kinase activity.

Cytoplasmic receptors are complexed to chaperone (or "heat

shock") proteins, inducing a conformational change in these

receptors.

List the types of hormones associated with the following types of nuclear receptors:

• primarily nuclear
• mainly cytoplasmic
• bound to DNA (in nucleus)

ligand‐induced conformational change of the

receptor results in a change in conformation of the DNA, thus

initiating transcription.

• Activated nuclear receptors bind to sequence elements in the regulatory region of responsive genes
• activate or repress DNA transcription

• The many classes of G proteins, in conjunction w/ the presence of several receptor types for a single ligand, providea mechanism for diversity
• common signal can elicit the appropriate effects in different tissues 

1. G_s
2. G_i
3. G_q
4. G₁₂

Define G_s:

• stimulates Adenylate Cyclase. 
• Toxin from Vibrio cholerae activate it inintestinal epithelial cells & inc. Cl‐ conductance & water flow.

• hormone‐dependent inhibition of AC. 
• Bordetella pertussis (whooping cough) inactivates it, so AC cannot be inhibited.

• stimulate PLC to generate IP₃ and mobilize Ca²⁺ from internal stores

• regulation of the mitogen‐activated protein kinase (MAPK) cascade, like G_s and G_q

• A‐ Rhodopsin like
• B‐ Secretine like
• C‐ Metabotropic glutamate/pheromone
• D‐ Fungal pheromone
• E‐ cAMP receptors
• Ocular albinism proteins
• Frizzled/Smoothened Family

No b/c its the binding of a receptor; not in cell membrane

2nd messenger has to be intracellular

pathway 1: GPCR > phospholipase C > PIP₂ > DAG > PKC

pathway 2: GPCR > phospholipase C > PIP₂ > IP₃ > ER (which releases Ca²⁺)    

• Ras regulates oncogenesis
• Rho rearrangement of the actin cytoskeleton
• Rab and Arf, regulate vesicle trafficking

1. Cyclic Nucleotides (cAMP signal pathway): Adenylyl Cyclase (AC), Protein Kinase A, and cAMP phosphodiesterase.
2. Products of Phosphoinositide breakdown (IP3 signal pathway that releases Ca+2)
3. Arachidonic Acid (AA) metabolites (eicosanoids)

• cAMP usually exerts its effect by increasing the activity of PKA.
• transfers ATP to certain serine or threonine residues 

PKA phosphorylation of the Beta₂‐adrenergic receptor

causes what?

• cGMP exerts its effect by stimulating a nonselective cation channel in the retina
• cGMP is important in signal transduction of light in retina; opens channels in retina

• ligh activates a GPCR called rhodopsin
• which activates the G protein transducin
• which in turn activates the cGMP phosphodiesterase that lowers [cGMP]_i

• the fall in [cGMP]_i closes cGMP-gated nonselective cation channels that are members of the same family of CNG ion channels (cyclic nucleotide-gated ion channels) that cAMP activates in olfactory signaling 

• minor constituents of cell membranes
• largely distributed in internal leaflet of membrane 
• play an important role in signal transduction

1. binding of hormone to cell surface GPCR activates phospholipase C_β
2. phospholipase C_β hydrolyzes PIP₂ into IP₃ and DAG (PLC leaves the polar head of PIP₂)
3. IP₃ interacts w/ a receptor in the membrane of the ER, which allows the release of Ca²⁺ into the cytosol
4. the SERCA Ca²⁺ pump transports the Ca²⁺ back into SR

Give the characteristics of Inositol 1,4,5-trisphosphate

(IP3); i.e. what does it act through, stimulate, & mediate, etc.:

• acts through G proteins
• water-soluble IP₃ stimulates intracellular Ca²⁺ release
• IP₃ receptor (ITPR) is ligand-gated Ca²⁺ channel in ER
• mediates a rapid rise in free cytosolic Ca²⁺ conc.
• ATP-fueled Ca²⁺ pump (SERCA) moves Ca²⁺ back into ER

• acts through G proteins 
• activates PKC
• production of DAG comes from phosphatidycholine (PC) either directly (by PLC) or indirectly (by PLD)
• some DAGs can be further cleaved by DAG lipase to arachidonic acid & eicosanoids

• Tumor necrosis factor α (TNF‐α)
• Interleukin 1 (IL‐1)
• Interleukin 3 (IL‐3)
• Interferon α (IFN‐α)
• Colony‐stimulating factor

• agonist binds to a membrane recptor
• this activates a G protein which stimulates PLA₂ either directly or through MAP kinase

• serotonin (5‐HT2 R)
• glutamate
• FGF‐ß
• IFN‐alpha
• IFN‐gamma

• agonists act on other receptors such as dopamine, adenosine, N-E, & serotonin (5-HT1 R)

1. Bind to a receptor coupled to PLC, which would lead to the release of DAG and DAG lipase can cleave DAG to yield AA and a MAG.
2. Agonist that raises [Ca²⁺]_i can promote AA formation because Ca²⁺ can stimulate some cytosolic forms of PLA₂
3. Signal transduction pathway that activates MAP kinase can also enhance AA release because MAP kinase phosphorylates PLA₂.

• PLA₂ promotes AA
• A series of enzymes convert AA into eicosanoids
• these enzymes are  COX, LOX, and Epoxygenase

1. Cycloxygenase (COX): thromboxanes, prostaglandins, and prostacyclins
2. 5-lipoyxygenase (LOX): leukotrienes & some hydroxyeicosatetraenoic acid (HETE)
3. Epoxygenase enzymes (members of the cytochrome P-450): HETE as well as cis-epoxyeicosatrienoic acid (EET) compounds

COX1: constitutive (always present)

• Inhibited by Aspirin.
• platelet aggregation
• regulation of vascular tone (vasodilation or vasoconstriction)
• cytoprotection in gastric mucosa

• Thromboxane A₂: Aggregate platelets, & constrict small vessels.
• Prostacyclin I₂: Inhibits platelet aggregation & dilates vessels. (opposite of thromboxane A2)
• Prostaglandins: platelet aggregation, airway constriction, renin release, inflammation, & mechanisms of cancer, cardiovascular & inflammatory diseases. (why asthma patients can't have aspirin)

• mediate allergic, inflammatory responses & anaphylaxis (LT & some HETE)
• LOX metabolites can influence activity of many ion channels (either directly or by regulating protein kinases)
• eg. dec excitability of cells by activating K⁺ channels & prevents excess insulin secretion by inhibiting CaM kinase II

HETE

• enhance intracellular Ca²⁺ release
• enhance cell proliferation

EET

• enhance release of intracellular Ca²⁺, Na⁺-H⁺ exchange
• enhance cell proliferation
• in blood vessels, EETs cause vasodilation & angiogenesis (creation of new blood vessels)

Which of the following are considered second messengers?

1. Dyacylglycerol
2. Thromboxane
3. Calcium
4. All of the above
5. none of the above

• senses changes w/ sensory receptors 
• interprets & remembers those changes
• reacts to those changes w/ effectors (i.e. muscular contractions & glandular secretions)

bundle of hundreds or thousands of axons,

each of which courses along a defined path and serves a

specific region of the body

• 12 pairs CN emerge from the base of the brain
• 31 pairs SN emerge from the spinal cord, each serving specific region of the body

• SOMATIC - voluntary; neurons from cutaneous & special sensory receptors to CNS; motor neurons to skeletal muscle tissue (effectors)
• AUTONOMIC - involuntary; sensory neurons from visceral organs to CNS; motor neurons to smooth & cardiac muscle & glands
• ENTERIC - involuntary sensory & motor control gastrointestinal tract; neurons function independently of ANS & CNS

• sympathetic - speeds up heart rate
• parasympathetic - slows down hr

• single nucleus with prominent nucleolus
• nissl bodies
• neurofilaments give shape & support
• microtubules move material inside cell

• conduct impulses TOWARDS cell body
• short, highly branched, & unmyelinated
• surfaces specialized for contact w/ other neurons
• contains neurofibrils & nissl bodies

• conducts impulses AWAY from cell body
• long, thin cylindrical processes
• impulses arise from initial segment (trigger zone)
• side branches (collaterals) end in axon terminals
• swollen tips (synaptic end bulbs) contain vesicles filled w/ NTs

1. action potentials that can travel long distances
2. graded potentials that are local membrane changes only

in living cells, flow of ions occurs through ion channels in cell membrane

The propagation of electrical signals (depolarizations &

hyperpolarizations) in the NS involves what kind of currents? What does this depend on?

• involves local current loops or local circuit currents
• depends on nature of conducting & insulating medium
• (electrotonic spread of electrical signals not limited to excitable cells)

• hyperpolarization = membrane becoming more negative
• depolarization = membrane becoming more positive

signals are graded (vary in amplitude/size depending on strength of stimulus) & localized

• mechanical stimulation of membranes w/ mechanical gated ion channels (pressure)
• chemical stimulation of membrane w/ ligand gated ion channels (NT)

ions flow through ion channels & change membrane potential LOCALLY. (amt of change varies w/ stimuli strength)

An action potential (AP) or impulse is a sequence of rapidly

occurring events that does what?

• increases & eventually reverses the membrane potential (depolarization) & then restores it to the resting state (repolarization).
• during AP, voltage-gated Na⁺ & K⁺ channels open in sequence

According to the all‐or‐none principle, if a stimulus reaches

threshold, the action potential is always...?

the same

(a stronger stimulus will not cause a larger impulse; travels/spreads over surface w/o dying out)

• Na⁺ rushes in (depolarization)
• K⁺ rushes out (repolarization)

• usually generated at axon hillock (where current depolarizes neighboring region of axon membrane)
• APs travel only in ONE direction: toward synaptic terminal
• Inactivated Na⁺ channels (refractory period) behind the zone of depolarization prevent the action potential from traveling backwards

• increasing the diameter of the axon
• myelination or electrical insulation

The density of voltage‐gated Na⁺ channels is very high in the

nodal membrane and conserves ionic concentration

gradients. It is maintained at the expense of ATP hydrolysis

by the Na+/K+ pump.

Electrical signals must pass across the specialized gap region

between two apposing cell membranes that is called a...?

• electrical (gap junctions that allow flow of ions)
• chemical (NTs)

The interface between the motor neuron and the muscle cell is

called what?

• adj. cell membrane separated by 3 nm & nearly sealed by gap junction (how ionic current spreads to next cell)
• faster, two-way transmission, capable of synchronizing
• found in cardiac & smooth muscle but are rare in mammalian NS

• adj. cell membrane separated by much larger distance of 30-50 nm
• NTs  provide electrical continuity b/n adj. cells
• one-way info transfer from presynaptic neuron to post-synaptic
• synaptic delay 0.5-1 msec

1. voltage-gated Ca²⁺ channels open
2. Ca ²⁺ flows inward triggering release of NT from presynaptic membrane (SNARE proteins)
3. NT crosses synaptic cleft & binding to postsynaptic cell ligand-gated receptors 

The binding of the neurotransmitter to the receptor is finite

and is determined by what?

Only the ______ neurotransmitter will produce the desired

response

The ion channels return to their resting state when the

__________ is no longer activated.

1. ligand-gated ion channels
2. G-protein coupled receptors

activation of an ionotropic receptor causes rapid opening of ion channels

 nicotinic AChR neuromuscular junction of skeletal muscle (activates muscle fiber)

1. enzymatic destruction of NT (hydrolysis of ACh by acetylcholinesterase)
2. uptake of NT into presynaptic nerve terminal or into other cells (neuron or glia) by Na⁺ dependent transport system
3. diffusion of transmiter molecules away form synapse (move down conc. gradient)

Direct synaptic transmission involves binding of

neurotransmitters to _________________ in the

postsynaptic cell

Direct synaptic transmission involves binding of

neurotransmitters to ligand‐gated ion channels in the

postsynaptic cell

Neurotransmitter binding causes ion channels to

open, generating a...?

• depolarizing postsynaptic potential
• results form opening of ligand-gated Na⁺ channels
• postsynaptic cell more likely to reach threshold
• graded potential that spreads decrementally away from synapse by local current

• hyperpolarizing postsynaptic potential 
• results from opening of ligand-gated Cl^- or K⁺ channel; (inc. in permeability to Cl^- doesn't change mem potential)
• graded potential that causes postsynaptic cell to become more negative & less likely to reach threshold
• may be no IPSP but stabilization of mem potential at existing value

In the CNS, receptor‐gated channels for _______ and

__________ are cation selective and give rise to depolarizing excitatory postsynaptic potentials.

In the CNS, receptor‐gated channels for serotonin and

glutamate are cation selective and give rise to depolarizing

excitatory postsynaptic potentials.

The receptor‐gated channels for ______ and

_____ are anion selective and drive V_m in the hyperpolarizing direction, toward the equilibrium potential for Cl^‐. These hyperpolarizing postsynaptic responses are called inhibitory postsynaptic potentials.

the receptor‐gated channels for glycine and

GABA are anion selective and drive Vm in the hyperpolarizing

direction, toward the equilibrium potential for Cl‐. These

hyperpolarizing postsynaptic responses are called inhibitory

postsynaptic potentials.

1. Small EPSP occurs (potential reaches -57 mV only)
2. Impulse is generated (threshold reached; mV at least -55)
3. IPSP occurs (membrane hyperpolarized; potential drops below -70 mV)

• Many synapses may have input to a single post‐synaptic neuron
• info brought in & influences cell activity

• one pre-synaptic neuron may have input to many post-synaptic neurons
• info is disseminated to many pathways & influence many systems

depends on the number of synapses active at any one time & the number that is excitatory or inhibitory

____________ cells are not usually stimulated to threshold by

one excitatory event.

Postsynaptic cells are not usually stimulated to threshold by

one excitatory event.

example: one EPSP may only generate 0.5 mV, whereas in

order to depolarize the neuron to threshold it requires about

15 mV.

If several presynaptic end bulbs release their

neurotransmitter at about the same time, the combined

effect may generate a nerve impulse due to what?

summation

(postsynaptic neuron is an integrator receiving & integrating signals then responding)

• when a neuron is stimulated to produce an EPSP & a 2nd EPSP is generated before 1st EPSP has returned to base line
• 2nd EPSP adds to previous EPSP & produces greater depolarization than single EPSP
• input signals arrive at the same time @ different times

• when 2 EPSP from location on different cells or two inputs occur @ different location on same postsynaptic neuron 
• also produces summation effect in postsynaptic neuron

If the excitatory effect is greater than the inhibitory effect but

less that the threshold level of stimulation, the result is what?(makes it easier to generate a nerve impulse)

If the excitatory effect is greater than the inhibitory effect and

reaches or surpasses the threshold level of stimulation, the

result is what?

Excitatory Postsynaptic Potentials and Inhibitory Postsynaptic

Potentials generate opposing currents, when they occur at the

same time cancel each other, resulting in what?

In a cell with V_m of -70 mV that receives 2 EPSP producing a V_m change of +10 mV (total for both) and 1 IPSP with V_m change of -5 mV. What term defines V_m change?

A presynaptic terminal does not release a fixed amount of

neurotransmitter for every impulse, since the release

depends on the concentration of what?

• the fact that synaptic events (excitatory or inhibitory) are variable or constantly changing
• effectiveness of given synapse may be influenced by presynaptic & postsynaptic mechanisms
• calcium levels (pumped into cell during AP & pumped out of cell/organelles)

• specialized synapses b/n motor neurons & skeletal musc. 
• aka end plate 
• motor neuron w/ cell bodies in spinal cord have long axons that branch to innervate sep. fibers of sk. muscle

______________ form a cap over the face of the nerve

membrane that is located _____ from the muscle membrane.

Schwann cells form a cap over the face of the nerve

membrane that is located away from the muscle membrane.

• modify postsynaptic response to NTs by attenuating or augmenting synaptic activity to specific NT
• take place over long period of time (long duration & low concentration)
• associated with slow events like learning, development, motivational states, & sensory/motor activity

• take place in millisec; involved in rapid communnication
• both excitatory & inhibitory NTs present in CNS & PNS (same NT can be excitatory in some locations & inhibitory in others) 

1. synthesis = stimulated or inhibited
2. release = blocked or enhanced
3. removal = stimulated or blocked
4. receptor site = blocked or activated 

• ligand-gated ion channels
• action is immediate & brief
• excitatory receptors are channels for small cations
• Na⁺ influx contributes most to depolarization
• inhibitory receptors allow Cl^- influx or K⁺ efflux that causes hyperpolarization

• Transmembrane protein complexes
• Neurotransmitter binds to G protein–linked receptor
• G protein is activated, producing second messengers, e.g., cyclic AMP, cyclic GMP, diacylglycerol or Ca²⁺
• Responses are indirect, slow, complex, and often prolonged & widespread

muscarinic ACh receptors and those that bind

biogenic amines and neuropeptides

• Open or close ion channels
• Activate kinase enzymes
• Phosphorylate channel proteins
• Activate genes and induce protein synthesis

ACETYLCHOLINE

• Vertebrates have 2 major classes of ACh receptors, one ligand-gated and one metabotropic

• ACh is synthesized from acetyl coenzyme A & choline
• stored in synaptic vesicles until a stimulus triggers release

After ACh is released and activates the receptor on the

postsynaptic membrane, it is metabolized by what?

• desensitization 
• weakness or loss of muscle tone

• ACh-esterase degrades ACh
• inhibitors include nerve agents and pesticides

• agonists: nicotine, physiostigmine
• antagonists: curare, atropine (mydriasis)

• initial steps in cat. synthesis begins w/ tyrosine
• tyrosine taken up by axon terminal then converted to L-Dopa
• this conversion that passes BBB by enzyme tyrosine hydroxylase is the rate limiting step
• further conversion to norepinephrine

*the Cat's in the DEN*

• Dopamine
• Epinephrine
• Norepinephrine

(Cate likes to live dangerously, don't need epinephrine)

L-Tyrosine > tyrosine OHlase > L-DOPA > DOPA decarboxylase > Dopamine > dopamine beta- OHlase > Norepinephrine > phenylethanolamine & N-methyl transferase > Epinephrine