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NROB60 Exam With Complete
Solution
Action Potential Answer Dramatic redistribution of electrical charge across membrane. Rapid reversal of charge across membrane such that the interior becomes relatively positive (depolarization caused by influx of sodium)
How to determine MP Answer Microelectrode in cell, voltmetre used to measure electrical potential between tip of intracellular and extracellular microelectrode
Membrane potential at rest Answer ~-65mV
Key parts of Action Potential Answer Rising phase, overshoot, falling phase, undershoot/after-hyperpolarization, restoration of resting potential
Length of Action Potential Answer ~2msec
Rising Phase Answer Rapid depolarization of membrane until ~40mV; Na+ rush into cell through open Na channels
Overshoot Answer Section of AP where inside positively charged wrt outside; MP goes to value close to ENa+ (greater than 0) because relative permeability of membrane greatly favours sodium
Falling Phase Answer rapid repolarization (efflux of potassium) until membrane more negative than resting potential (undershoot); result of Na+ channel inactivation, K+ channels opening, K+efflux.
Perception of Sharp Pain (thumbtack) Answer 1. Thumbtack enters skin
- Membrane of nerve fibres in skin stretched
- Na+ permeable channels open, Na+ ions enter nerve fibre down [gradient]
4.entry of Na+ depolarizes membrane; depolarization reaches threshold potential; ACTION POTENTIAL!
"all or none" Answer Increasing depolarization has no effect until crossing threshold
Multiple Action Potentials: Rate and Frequency Answer Rate depends on magnitude of continuous depolarization
Frequency reflects magnitude of depolarization current (max: 1000Hz)
Absolute Refractory Period Answer ~1msec; impossible to initiate another AP; Na
Channels must be de-inactivated by sufficiently negative MP
Relative Refractory Period Answer several msec; relatively difficult- amount of current required for depolarization to threshold elevated (result of hyperpolarization/undershoot)
Intracellular Recording Answer impale neuron w microelectrode; challenging (SIZE); goal is to measure potential difference between intracellular electrode and grounded electrode; I. Electrode filled w concentrated KCl; potential difference between electrode and ground displayed w oscilloscope
Extracellular Recording Answer Detecting sequence of ionic movements across neuronal membrane by placing electrode near membrane; when AP arrives at recording position, +ve charges flow away from recording electrode into neuron; as AP passes by, +ve charges flow out across membrane towards recording electrode; EC AP characterized by brief, alternating voltage difference between recording electrode and ground. Voltage changes seen w oscilloscope, heard by connecting output to loudspeaker (Popping sound)
Concentration Gradients Answer Na-K pumps continuous work to establish and maintain concentration gradients; K+ efflux until inside -ve and Vm=Ek. Net movement of K+ is electrical current (Ik); # K+ channels open proportional to electrical conductance (gk)
Ik=gk(Vm-Ek)
Ideal Neuron Answer Only permeable to K+; Vm=Ek=-80mV
Action Potential in Reality Answer When membrane depolarized to threshold; transient increase in gNA-> entry of Na+, depolarizes neuron. Return to RP by transient gK increase during falling phase.
Voltage Clamp Answer Kenneth C. Cole; Hodgkin and Huxley could Clamp at any chosen MP Value
Showed rising phase of AP caused by transient increase in gNa, influx of Na+; falling phase associated w increase in gK, efflux in K+
Voltage Gated Sodium Channel Answer Protein forms pore in membrane that is highly selective to Na+ ions; pore is opened and closed by changes in Electrical potential of membrane
Sodium Channel Structure Answer Single long polypeptide; 4 distinct domains (I-IV); Each domain made of 6 transmembrane alpha helices (S1-S6); domains clump together to form pore between them; pore loops assembled into selectivity filter (12x more permeable to Na+ than K+); Voltage sensor in S4- +ve aa residues regularly spaced along helix coils, depolarization twists S4 causing gate to open
Patch Clamp Answer Method of studying ionic currents passed through individual ion
Voltage Gated K+ Channel Structure Answer 4 separate polypeptide subunits that come together to form pore between them; proteins sensitive to changes in electrical field across membrane- when depolarized, subunits believed to twist into shape allowing K+ to pass through
Action Potential Conductance Answer 1. axon depolarized to reach threshold, Na+ channels open, AP Initiatied
- influx of +ve charge depolarizes segment of membrane immediately before reaching threshold and generates own AP
- AP works down axon until reaching terminal
AP Conductance Characteristics Answer -Propagates in only one direction (can be generated in either, but doesn't revert back)
-membrane behind AP is refractory
-forward propagation = orthodromic
-backwards propagation= antidromic
-propagation occurs without decrement
-typical rate is 10m/sec
Factors influencing conduction velocity Answer if axon narrow, many open pores, most of current will flow out
axon wide, few open pore, current will flow down
increasing velocity w increasing axonial diameter
myelination
Local Anaesthesia Answer temporarily blocks action potentials in axons; small axons most susceptible (less of a safety margin, more channels must function to ensure AP doesn't fizzle)
1st local anaesthetic Answer Cocaine (still #1 in my heart eyyyy)
Lidocaine Answer most widely used Local Anaesthetic. binding site- S6 alpha helix of domain IV of protein. Cannot gain access to this site from outside; must first cross axonal membrane then pass through open gate... therefore why active nerves blocked faster
Topical Anaesthesia Answer dissolved into jelly, smeared on mucous membranes
Infiltration anesthesia and nerve block Answer injection into tissue
injection into nerve
Spinal Anaesthesia Answer infused to CSF bathing spinal cord (large parts of body)
Myelin and Saltatory Conduction Answer Myelination increases AP conduction velocity--> APs skip node to node
Multiple Sclerosis Answer MS attacks myelin sheaths of nerve bundles in Brain, Spinal Cord, Optic Nerves
characterized by marked slowing of conduction velocity of optic nerve
MS Test Answer stimulate eye w checkerboard pattern, measure elapsed time till electrical response occurs (scalp over part of brain that is target of optic nerve)
Guillain-Barre syndrome Answer more common than MS, attacks myelin of peripheral nerves innervating muscles and skin.
may follow minor infectious illnesses and innoculations, appears to result from anomalous immunological response against one's own myelin
demonstrated clinically by stimulating peripheral nerves electrically through skin, measuring response time
Dendrites/Somas and APs Answer no channels= no AP unless synaptic input from other neurons.
Spike initiation zone Answer Axon hillock
Stellate Cell and AP Answer typically responds to steady depolarizing current injected into its soma by firing APs at relatively steady frequency through stimulus
Pyramidal Cell and AP Answer cannot sustain steady firing rate; fire rapidly at beginning of stimulus then slow down, even if stimulus remains strong
Adaptation Answer slowing over time (common property of excitable cells)
Burst Answer rapid cluster of APs followed by brief pause
Synaptic Transmission Answer process of info transfer at synapse
(adhere pre and post synaptic neurons to each other)
Presynaptic Element Answer usually axon terminal, typically containingdozens of synaptic vesicles and secretory granules (containing soluble protein that appears dark in electron microscope; dense core vesicles)
Membrane Differentiations Answer dense accumulations of proteins adjacent to and within membranes on either side of synaptic cleft
Active Zones Answer actual sites of neurotransmitter release on presynaptic side; proteins jutting into cytoplasm on terminal along intracellular face of membrane
Postsynaptic Density Answer protein thickly accumulated in and just under postsynaptic membrane, contains neurotransmitter receptors; convert signal
Axodendritic Synapse Answer postsynaptic membrane on dendrite
Axosomatic synapse Answer postsynaptic membrane on soma
Axoaxonic synapse Answer postsynaptic membrane on axon
dendritic spines Answer dendrites synapse with other dendrites
Gray's type I synapses Answer membrane differentiation on postsynaptic side thicker than on presyn side- ASYMMETRICAL. Usually excitatory (Glutamate)
Gray's type II synapses Answer membrane differentiation of similar thicknesses- SYMMETRICAL. Inhibitory, GABA/gly
Neuromuscular Junction Answer chemical synapses between axons of motor neurons of
spinal cord and skeletal muscle. Many structural features of cns chemical synapse. AP in motor axon= AP in muscle cell
Neuromuscular Junction structural specializations Answer SIZE- one of largest synapses in body
Presyn terminal contains large # active zones
Post-syn membrane (motor end plate) contains series of shallow folds packed w neurotransmitter receptors- active zones align w junctional folds, ensure many nt molecules focally released onto large surface of chemically sensitive membrane
Neurotransmitter Categories Answer Amino Acids; Amines; Ppetides
Amino Acid nts Answer small organic molecules, min 1 N atom, stored in and released from synaptic vehicles. Fast synaptic transmission at most CNS synapses mediated by Glu, GABA, Gly
Amine nts Answer small organic molecules, min 1 N atom, stored in and released from synaptic vehicles. Ach, DA, Epinephrine, Histamine, NE, 5-HT
Peptide nts Answer large molecules stored in and released from secretory granules. CCK, Dynorphin, Enk, NAAG, Neuropeptide Y, Somatostatin, Substance P, Thyrotropin-releasing hormone, VIP
Nt synthesis/storage Answer Gly, Glu: aa, abundant in all cells
GABA, Amines: made only by neurons that release them (specific enzymes), transported to axon terminal and taken up into synaptic vesicles
Peptides: aa strung together by ribosomes of cell body; synthesised in rough ER, split in golgi apparatus (from where secretory granules bud off)
Nt release Answer arrival of AP in axon terminal= voltage gated Ca channels in active zones to open= influx of Ca2+=exocytosis of vesicles/granules (release of peptides requires high frequency trains of AP, slow compared to release of other nts)
messengers) that diffuse away in cytosol (can activate additional enzymes in cytosol that can regulate ion channel function and alter cellular metabolism) Metabotropic receptors.
Autoreceptors Answer presynaptic receptors sensitive to nt released by presyn terminal; typically G-protein-coupled-receptors that stimulate second messenger formation. allows presyn terminal to regulate itself. (safety valve)
nt recovery/degredation- presynaptic membrane Answer diffusion away from synapse, aided by reuptake into presyn axon terminal (specific nt proteins located in presyn membrane). Once uptaken, may be enzymatically destroyed or recycled.
nt recovery/degredation- glia/synaptic cleft Answer nt transporters into glia, enzymatically degraded. enzymatic degredation in cleft too (eg. ACh)
Desensitization Answer uninterrupted exposure to nt ( ACh at neuromuscular junction). persist for many seconds after nt removed
Reversal Potentials Answer many trans-gated-ion-channels not permeable to single ion type. eg. ACh channel permeable to Na+ and K+. if equally permeable, current would bring MP towards 0. critical value of MP at which direction of current flow reverses = reversal potential. if nt causes Vm(MP)> AP threshold, excitatory. if <, inhibitory.
Neuropharmacology Answer study of effects of drugs on nervous system tissue
inhibitors Answer inhibit normal function of specific proteins involved in synaptic transmission
receptor antagonists Answer inhibitors of nt receptors which bind to receptors and block normal transmitter action
receptor agonists Answer bind to receptors and mimic naturally occuring nt actions
nicotinic ACh receptors Answer ACh-gated ion channels in muscle, also in CNS
Synaptic integration Answer process by which multiple synaptic potentials combine within one postsynaptic neuron
quantization Answer multiples of indivisible unit, reflect number of transmitter molecules in single synaptic vesicle and number of postsynaptic receptors available at synapse
miniature PSP Answer size of postsyn. response to spontaneously released nt, each mini generated by transmitter contents of one vesicle
quantal analysis Answer method of comparing amplitudes of mini and evoked epsps, can be used to determine how many vesicles release nt during normal syn trans. at neuromuscular junction = single ap triggers ~200 syn vesicles exocytosed --> EPSP 40mV or more
EPSP Summation Answer simplest form of synaptic integration in CNS
Spatial summation Answer add EPSP generated simultaneously at many diff synapses on dendrite
Temporal summation Answer same synapse, rapid succession (1-15msec of each other)
Dendritic Properties and Synaptic Integration Answer Dendritic Cable- 2 paths (down inside, down membrane). Dissipation across membrane= depolarization falls exponentially w increasing distance
Dendritic length constant (λ) Answer distance where depolarization is 37% that of origin; index of how far depolarization can spread down dendrite/axon (longer= more likely EPSPs will depolarize membrane @ hillock)
Strychnine poisoning Answer strychnine= powerful plant toxin, antagonist of gly
Milk poisoning: high doses nearly eliminate gly= mediated inhibition in circuits of spinal cord and brain stem= seizures, muscular contractions, spasm, respiratory paralysis, death. NO COGNITIVE IMPAIRMENT.
Modulation Answer synaptic activation of G-protein-coupled-nt receptors modifies EPSP effectiveness instead of directly evoking more. effect can last longer than presence of modulatory transmitter because it involves many intermediaries.
Modulation process Answer 1.) binding of amine nt NE to β receptor
2.) receptor activates G-protein that activates effector protein adenylyl cyclase
3.) catalyses ATP-> cAMP
4.) cAMP to stimulate protein kinase
5.) catalyze phosphorylation (eg. cause K channel to close, decrease K+ conductance, increase r(m) and therefore λ)
Cholinergic System Answer cells produce and release ACh
Noradrenic system Answer neurons use amine nt NE
Glutamatergic Synapses Answer synapses use glutamate
GABAergic Synapses Answer use GABA
Peptidergic Synapses Answer use peptides
3 criteria to be nt Answer 1.) must be synthesized and stored in presynaptic neuron
2.)must be released by presynaptic axon terminal upon stimulation
3.)when experimentally applied, must produce postsynaptic response mimicking
response produced by release of naturally occurring nt
Microionophoresis Answer method used to assess postyn. actions of transmitter candidate. Most nt candidates can be dissolved in solutions that cause them to get net electrical charge, then glass pipette filled w ionized solution, carefully positioned next to postsyn. membrane, ejected in small amounts. Effect measured by microelectrode.
Receptor subtype Answer each of the different receptors an nt binds to
Nicotine Answer receptor agonist in skeletal muscle, no effect in heart
Muscarine Answer little/no effect on skeletal muscle, agonist at cholinergic receptor subtype in heart
Distinguishing Receptor Subtypes Answer different agonists, antagonists
Cholinergic Receptor Subtypes Answer Nicotinic ACh receptor (agonist: nicotine; antagonist- curare)
Muscarinic ACh receptor (Agonist: muscarine; Antagonist: Atrophine)
Noradrenic Receptor Subtypes Answer Alpha NE Receptor (agonist- phenylephrine; antagonist: phenoxybenzamine)
Beta NE Receptor (Agonist: isoproterenol; antagonist: propranolol)
Glutamatergic Receptor Subtipes Answer AMPA (Agonist: AMPA, Antagoinist: CNQX)
NMDA (Agonist: NMDA; Antagonist: APS)
Opiates Answer broad class of drugs both medically important and commonly abused; effects include pain relief, euphoria, depressed breathing, constipation. AGONISTS at specific receptors in neuronal membranes
ACh Synthesis Answer ChAT synthesizes ACh in cytosol of axon terminal- transfers acetyl group from acetyl CoA to choline (from ECF, where exists in [low micromolar], taken up via transporter)
ACh synthesis Rate Limiting Step Answer transport of choline into neuron
AChE Answer manufactured by cholinergic neurons, secreted into synaptic cleft and associated w cholinergic acon terminal membranes; degrades ACh into choline and acetic acid, VERY QUICK; much resulting choline recycled.
AChE inhibition Answer prevents ACh breakdown, disrupting transmission. irreversible inhibition usually results in respiratory paralysis
Catecholamines Answer tyrosine creates 3 amine nts
Dopamine
Norepinephrine
Epinephrine
catecholaminergic neurons Answer found in regions of nervous system involved in regulation of movement, mood, attention, and visceral function
catecholamine synthesis Answer Tyrosine Hydroxylase catalyzes 1st step in (tyrosine-> dopa)
dopa converted into dopamine by dopa decarboxylase (abundant)
dopamine converted to NE by DBH (in synaptic vesicles)
NE to epinephrine by PNMT (back in cytosol)
catecholaminergic neurons rate limiting step Answer activity of TH (regulated by various cytosol signals)
catecholaminergic neurons- end product inhibitoin Answer decrease in catecholamine released by axon terminal causes catecholamine concentration in cytosol to rise, inhibiting TH
catecholaminergic neurons stop mechanism Answer selective reuptake via Na+ dependent transporters (Sensitive to many diff drugs)
recycled or enzymatically destroyed by MAO
Serotonin (5-HT) Answer tryptophan converted to 5-HTP by tryptophan hydroxylase
5-HTP to 5-HT by 5-HTP Decarboxylase
limited by tryptophan availability (from blood from diet)
same stop mechanism as catecholaminergic neurons (Amine)
serotonergic neurons Answer relatively few in number, important in mood, emotional behaviour, sleep
Glutamate/Glycine synthesis Answer aa from glucose
glutamatergic acon terminals Answer glutamate transporter concentrates glu until 50nM in synaptic vesicles
GABA Synthesis/ degredation Answer synth: large quantities by neurons that use as nt;
Glutamate made into GABA by GAD
Deg: selective reuptake; metabolized by GABA transaminase
ATP as transmitter Answer in vesicles (usually with classic nt), released like classic nt
distinguished by various properties:
pharmacology- which nts affect, drugs interact
kinetics of binding process- duration of effect
Selectivity- excitation or inhibation, ca2+ amounts
conductance- magnitude of their effects
Glutamate Gated Channels Answer mediate bulk of fast excitatory syn transmission;
AMPA channels permeable to Na+, K+, not Ca2+; net effect admits Na+
Coexist w NMDA
NMDA gated channels vs AMPA Answer NMDA permeable to Ca2+; inward ionic current through NMDA-gated Channels is voltage dependent
NMDA gated channel process Answer opens, Ca2+ and Na+ enter cell, k+ out
Mg block prevents other ions passing through NMDA channel
Mg2+ unclogs pore when membrane depolarized (usually follows AMPA activation); inward ionic current voltage dependent
GABA gated Channels Answer mediates most syn inhibition; Cl channel
benzodiazepines and barbituates each bind to own distinct site on outside face of GABAa channel
Benzos, ethanol, and Barbituates on GABAa channel Answer Benzos- increase frequency of channel openings
Ethanol- depends on specific structure (evidence that particular subunits are required)
Barbituates- increase duration of channel openings
Neurosteroids Answer natural metabolites of steroid hormones synthesized from cholesterol primarily in gonads, adrenal glands, glial brain cells; enhance/supress
inhibitory function; own site on GABAa receptor
G-Protein Coupled receptor structure Answer 7 membrane spanning alpha helices
2 EC loops form transmitter binding sites
2 IC loops can bind to/activate G proteins
General G-protein operation Answer 1.) 3-subunits (ɑ, β, and γ); Resting state- GDP bound to Gɑ, whole complex floats on membrane inner surface
2.) GDP bound protein bumps into proper type of receptor (w bound transmitter), GDP exchanged for GTP picked up from cytosol
3.)activated GTPbound protein splits into Gɑ plus GTP; and Gβγ complex
4.) Ga is an enxyme that eventually self terminates by converting GTP back to GDP
5.) Gβγ and Ga come back together, cycle restarts
Shortcut pathway Answer fastest of g-protein coupled systems responses beginning within 30-100msec of nt binding; v localized
Second Messenger Cascades Answer process that couples nts to activation of downstream enzyme
Second Messenger Cascade- NE β receptor Answer β receptor activates Gs
Gs stimulates adenylyl cyclase=> ATP to cAMP
cAMP increase activates PKA
activation of ɑ2 receptor activates Gi=> supress adenylyl cyclase
PLC Answer enzyme floating in adenylyl cyclase; acts on membrane phospholipid, splitting to DAG (lipid soluble, activates PKC) and IP3 (diffuses away in cyt., binds to IP gated ca channels on sER=> ca2+ discharge)
elecated Ca2+ activates CaMK; implicated in molecular mechanisms of memory
