neurophysiology for neurotransmitters part 1: excitability Flashcards
what is the current model of the cell membrane?
fluid mosaic model
what are channels
gated aqueous pores
the gates control whether ions can transverse pore.
what does a channel respond to?
gating stimulus (ie transmembrane volatage, binding of ligand, temperature, mechanical distortion of membrane)
what is part of the channel that determines which ions can move through the channel
selectivity filter
what do internal binding site in channel allow for?
internal binding site allow modulation of channel function by signalling pathways
what is current?
movement of charge
what carries charge in biological systems?
ions
what is a circuit element that resists charge?
resistor
relationship of conductance and resistance?
conductance = reciprocal of resistance
what is OHM’s Law?
V = IR
where V = voltage
I = current
R = resistance
what is equation for resistance?
Resistance = 1/G; G = conductance
what is a circuit element that can store charge?
capacitor
ion channels = what part of RC circuit
resistive elements (conductors of ions)
lipid bilayer = what part of RC circuit
insulator (cf dielectric of capacitor: stores charge= capacitance)
passive response = RC circuit
what is the consequence of the RC structure
electrical signals slowed by the capacitor(b/c it stores charge) —> membrane with time constant (time for membrane potential to fall to 1/e of original potential charge)
what does it mean if membrane semipermeable to ions?
permeable to some ions and not others
which ion are cells permeable to at rest?
K+
what maintains differen concentrations of the principal ion species?
what is membrane potential usually?
Na+/K+ ATPase
-70mV
if the membrane potential were only permeable to a single species, which equation would you use to find the equillibrium potential for that ion species?
Nernst equation: Eion = 61 log ([ion]outside/[ion]inside)
which equation predicts which ion species is dominating membrane permeability under a given set of circumstances?
Nernst
which equation predicts the membrane potential at equilibrium when all permeant ion speices are taken into account?
Goldman-Hodgkin-Katz equation
the electrogenic Na+/K+ ATPase that maintains membrane potential moves what?
3Na+ out for every 2K+ moved in
just know: Ca-ATPase transports Ca2+ ions across the cell membrane
the distributed geometry means of neurons means that not all membrane in he cell is ________at a given time
isopotential
passive conduction; cable properties
voltage is maximal at ___1______and the amplitude of the singal ___2____with distance from that point
- maximal at the point of stimulation
- amplitude of the signal decays exponentially with distance from that point (decay is symmetrican and bidirectional in uniform axon)
what is the time constant?
time for the singal to decay to 1/e of the maximum (where e is base of natural log =2.718). tme constant = characteristic of the gemoetry and properties of the cable. time constat longer for a larger diameter cable b/c there is a greater cross sectional area for charges to move along surface area
is time course slowed with distance? what is this due to?
yes. due to charge leaking across the membrane (and also to charging of the membrane capacitance). slowing of response is due to charging the membrane capacitance along the distributed cable.
at rest the cell membrane potential is ____________
polarized (inside of cell negative relative to outside)
make membrane more negative =
hyperpolarize
make membrane less negative =
depolarize
what is the stereotype response to stimuli that exceed the threshold potential?
this is an active response due to activation of voltage-gated ion channels
action potential
what is the voltage at which inward(depolarizing) current is just balanced by outward(hyperpolarizing current) any further depolarization leads to the all-or-none- AP response
Threshold
synonym for what happens upon repolarization and the membrane potential undershoots the original resting potential
afterhyperpolarization (AHP)
what are the two major types of neural electrical signals?
graded potentials and action potentials
what are passive responses (as predicted by an RC circuit). The amplitude of the response is proportional to the amplitude of the stimulus(linear relationship predicted by Ohm’s law).
graded potentials
what are examples of graded potentials?
receptor potentials( due to stimuation of a sensory receptor) and synaptic potentials( due to synaptic transmission)
;what are potentials that are described by active responses (voltage-dependent). they have a threshold, above which the amplitude of the response is all or one?
action potentials
upstroke of AP =
increse GNa+
downstroke of AP =
Na+ inactivation + incr GK+
undershoot or afterhyperpolarization of AP due to?
increased K+ conductance
REfractory period in AP
absolute =
relative =
absolute = Na+ inactivation
relative = incr GK+
three functional states of the Na+ channel?
closed
activated(open)
inactivated
describe the inactivated state of a Na+ channel
- continued depolarization causes open channels to pass into a 3rd state = inactivated state
- in inactivated state- no ions are conducted through the cannel and the cannel is not available to be acivated by another depolarization
- a finite time at a negative membrane potential (resting or more negative) is required in order to remove inactivation (transition from inactivated state to closed). only after channels are back in the closed state are they once again available to be activated.
what are the two states of the K+ channel?
closed and activated (open)
what is the difference btw the relative refractory period and the absolute refractory period?
relative refractory period = due to increaed K+ permeability(that also causes the afterhyperpolarization) followin the AP.
Absolute refractory period = no stimulus, no matter how large can elicit an AP b/c TOO MANY Na+ channels are in the inactivate stateto allow attainment of voltage threshold for an AP.
know: signaling via Action potentials allows rapid signaling, w/out decrement over distance. APs remain of the same amplitude b/c they are **regenerated in each patch of membrane that reaches threshold(APs are regenerative as well as all-or-none) **
know
t/f Action potentials are more efficient than graded (electronic or passive) at propagating signals over long distances
true
two ways to increase AP condution velocity?
- increase diameter
- myelin
in an axon, why is AP propagation unidirectional?
b/c of Na+ inactivation and resulting refractory period
how does myelin increase conduction velocity of an axon?
increases resistance of the membrane ions( since ions cannot pass through lipid and typically axons do not place channels in regions under myelin)
**decreased capacitance - less charge stored on the membrane so more charge is available to pass through axomplasm to next node of ranvier **
AP conductin in unmyelinated axon:
- how does charge propagate to the next patch of membrane?
- if depolarization reaches threshold, what happens?
- how is AP prevented from reversing its direction?
- conduction velocity of an unmyelinated axon is proportional to what?
- passively
- action potential
- Na+ inactivation causes refractory period –>prevents AP from reversing direction
- axon diameter (larger diameter–>greater velocity)
in _____axon, conduction velocity is increased by restricting the AP to the nodes of Ranvier and by facilitating electronic movement of charge between nodes
myelinated axon
larger axon diameters lead to more rapid conduction. which two types of neurons are the most rapidly conducting?
- Group 1 afferents
- alpha motorneuron axons
t/f. in mammalian myelinated axon, Na+ inactivation is more important than K+ activation for repolarizing APs.
true
in neurons the spike (AP) initiation zone is ither the______or _________ due to a combo of high Na+ channel density and geometric facotrs
- axon initial segment
- first node of ranvier
what happens in Multiple sclerosis?
loss of the myelin sheath of some axons(demyelination). underling mechanism is inflammation
what does loss of myelin initally lead to because Na+ channels are located too far apart for passive mechanisms to reulst in depol of the next group of channels?
conduction block (distribution can be remodeled, restoring some degree of axonal funtion)
describe alpha type and auxiallry subunits of the voltage gated Na+ channel
4 domains each with 6 transmembrane spanning regions with aqueous pore in between
what causes GEFS = generalized epilepsy with febrile seizures?
point mutations in the alpha subunit of Na+ channel that causes slowed inactivation of Na+ channels(the channels remain open too long —> hyperexcitability)
what causes myotonia (paramyotonia congenita) and periodic paralysis?
Na+ channel mutations in skeletal muscle
what is the structure of the voltage gated calcium channel alpha subunit/
4 domains of 6 transmembrane subunits
what causes Familial hemiplegic migraine?
mutation of the P/Q type Ca2+ channels (chaneel name: CaV2.2: gene name = CACNA1A)
what causes episodic ataxia type 2
due to truncation mutatnts of CAv2.2 Ca2+ channels
what cauases congenital stationary night blindness?
CSNB due ot truncated L-type Ca2+ channel (CAV1.4) in the retina (this alters sensitiviry of channels to modulation of calmodulin)
what causes Lambert-Eaton syndrome?
basically small cell carcinoma produce antibodies to voltage gated calicum channels (P/Q type as well as others) This AI activity alters the calcium channel function. clinical manifestation = dysfunction of the neuromuscular junction
what is myotonia?
myotonia = hyperexcitability of muscle that can be caused by mutations in a voltage gated Cl- channel. Unlike neurons, skeletal muscle has alot of Cl - permeability at rest (Cl - contributes to resting potential)
-resting membrane potential of muscle fibers becomes relatively depolarized making them more excitable.
which mutation responsible for benign familial neonatal seizures:
mutation of KCNQ2, a gene encoding a voltage-gated K+ channel (Kv7.2)
which mutation responsible for episodic ataxia type 1?
**mutations in the Kv1.1-type potassium channel in Purkinje cells **
t/f. mutations in other K+ channels also leads to seizure disorders.
true
