what 3 things did hodgkin and huxleys voltage clamp experiement predict?
1. sepearete na and k channels
2. voltage sensors in channels
3. high conductance of channels to specific ions
what happens once the patch clampvoltage reaches + 52 mv
early inward Na current is missing
what happens once the patch clampvoltage reaches + 65+ mv
early inward Na reverses to outward instead of inward
outward K current increases in magnitudie as the the voltage becomes more
patch clamp technieque records
microscopic currents (current flowing through a single membrane channel due to depolarization)
what are macroscopic currents due to?
current flow through may channels
what did patch clamp recording show?
provided evidence for single channels
in channels, there is a fast switch between
open and close states
In response to depolarizing effect from the pipette, single channels open and close in a ____ fashion
all or none fashion that is random or stochastic in nature
what does the probability of opening a channel depend on?
depolarization increases the proability a channel will be opened
what is gating? what does it involve?
gating is the transition between open and closed states
involves a temporary conformational change in the channels structure
what does macroscropic current arise from?
the aggregate effects of THOUSANDS of microscopic currents
there is a close correlation of the____ of macroscopic and the sum of many trials of microscopic currents
what is different about K channel and Na channel properties?
K channels have longer latency time and longer duration
also obviously different dierection
(Na on left, K on right)
on average the K+ channels tend to be an ____ state while the membrane is depolarized
open state (this results in a more sustained response)
most cns neurons ahve multiple ___ channels with different characteristics
charactersitics that vary with K channels
1. low voltage vs. high voltage activation (voltage dependence)
2. how fast the population reaches maximum conductance (rate of activation)
3. how fast they inactivate (some dont even inactivate)
what is important about the varying rates of K channel inactivation
produce a diversity of spike waveforms and spike patterns for different cells
Fast AHP ____ action potential
FAST AHP involves ___ repolarization
when does fast AHP affect the early spike frequency
at very high frequencies
what does medium AHP control
controls early interspike interval
what does medium AHP control
1. early spike frequency adaption (slowly activating by Ca entry)
2. late spike frequency adaption
BK K+ channels have ___ inactivation
___ and ___ are nonainactivating K channels
IK and SK
what do slow AHP do?
limits firing frequency by an unkwnon channels
order of channel activation
what is the order of K channel activation
1. Ka and Kdr channels first open
2. Kbk channels open
3/ other known and unknown K channels open
large number of ion channel genes create neurons with diverse ___
fast AHP occurs in ___ seconds
medium AHP occurs in ___ seconds
slow AHP occurs in ___ seconds
inactivation pattern of Kv2.1 channels?
show little inactivation
inactivation pattern of Kv4.1 channels?
inactivate rapdily after depolarization
when do inward rectifers allow more current flow?
why do so many genes encode K+ channels?
activation, gating, inactivation
shape complex electrical responses influence
1. duration of AP
2. resting membrane potential
TheC a++ activated K+ channel opens in response to
increasedintracellularCa++ and sometimes to membrane depolarization.
the ___ of ion channels is key to developing new therapeutics for CNS disorders
what do channelpathies result from?
they happen due to mutations in channel genes
channelpathies in voltage gated Ca channels
congential stationary night blindness
familial hemiplegic migraine
episodic ataxia type 2
channelpathies in Na channels
generalized epilepsy with febrile seizures
channelpathies in K channels
benign familial neonatal convulsion
channelpathy that causes congential stationary night blindness
channelpathy that causes generalized epilepsy with febrile seizures
channelpathy that causes familial hemiplegic migraine
channelpathy that causes benign familial neonatal convulsion
what toxins block Na channels?
ttx and saxitoxin
what toxins inactivate Na channels?
what does a-toxin do?
prolongs the duration of Na channels
what does b-toxins do?
shift voltage activation of Na channels
which toxins blod K channels?
apaminin (bees) and dendrotoxin (wasps)
what does TEA block?
K channels and AcH receptors
What blocks Ca channels?
ω-conotoxins (cone snails) and ω-agatoxin (spiders) block Ca channels
active ion transports work ___ a electrochemical gradient
how do active ion transporters and channels differ?
active ion transporters having slow binding and unbinding
also are slower transport than channels
w-conotoxins blocks ___ channels
n type Ca
w-agatoxin blocks ___ channels
P/Q type Ca channels
____ form a compelx with the ion they transport
active ion transporters
how do ion exchangers work?
they don't use energy
but trade an intracellular ion for an extracellular one
how do ion co-transporters work?
transport two or more moelcules in the SAME DIRECTION ACROSS A MEMBRANE
methods in determining channel type?
1. patch clamp technique
2. gene cloning
3. x ray crsytallography