PHYSL 371: Voltage-gated Na+/K+ Channels

Ohm's law formula

V=IR

V= voltage

I= current

R= resistance

what does Ohm's law measure

the relationship between resistance in any system and how that governs the size of the current you see in response to a voltage gradient

voltage

difference in electrical energy between two points

current

the flow of electrical charge

resistence

the materials in opposition to the flow of the current

conductance

the degree to which an object conducts electricity aka the movement of ions through a channel (inverse of resistance)

conductance formula

G=I/V (the current at any given voltage)

G= conductance

I= current

V= voltage

what happens to current as the conductance of a channel increases

you will get a larger current

modified Ohm's law

I=(G)(V)

G in modified Ohm's law

macroscopic conductance

(g)(N)(Po)

V in modified Ohm's law

voltage (describes the size and direction of the electrochemical gradient)

(Vm)-(Ex)

N in modified Ohm's law

Number of channels in the membrane

-each channel can switch between open and closed

-the more channels that are present, the larger the current

-positive number

Po in modified Ohm's law

probability/likelihood a channel will be open

-equilibrium that depends on the presence of a stimulus for the channel

-ex. for voltage gated channels, a strong voltage increases Po while a weak voltage decreases Po

-value between 0-1

g in modified Ohm's law

unitary (single channel) conductance

-the slope of a voltage current graph is the conductance of a channel

- size of conductance varies depending on the channel type

-the direction of conductance of ion also depend sings on the type of channel

relationship between voltage current graphs

size of currents depends on voltage in a linear way

inward current

flow of cations into the cell when the channel is open

outward current

flow of cations out of the cell when the channel is open

microscopic recordings on a chart

repeating the same stimulus on multiple channels or the same channel will result in fluctuations between recordings

macroscopic recordings on a chart

the overall conductance of a cell gives a uniform smooth recording by adding all the individual recordings together

Vm-Ex

driving force of an ion which describes what direction it will move in or out of the cell when the channel is open

what happens when Vm is greater than Ex

positive driving force (outward current)

what happens when Ex is greater than Vm

negative driving force (inward current)

current voltage (I-V) relationship of K+

1. at negative voltages the channels are closed and current is zero

2. as voltage increases, channels will open and current will steeply increase

3. when voltage is equal to zero, all the channels will be open and current will increase linearly with voltage

what 2 things change as voltage increases in a V-I relationship

the number of channels open and the electrochemical driving force

conductance voltage (G-V) relationship of K+

1. at negative voltages conductance is low because channels are most likely closed

2. as voltage increases, conductance increase steeply as the number of channels open increase

3. at positive voltages, conductance levels off a high value because most of the channels are open at that point

(sigmoidal graph)

what is the difference between a G-V and a I-V graph

the G-V graph divides the size of the current by the DF at each voltage in order to describe the activity of an ion channel changing in response to voltage

current voltage (I-V) relationship of Na+

1. at negative voltages the channels are closed and current is zero

2. as voltage increases, the channels start to open and current steeply decreases because Na+ flow into the cell (inward current)

3. when voltage becomes zero, most of the channels are open and current increases linearly

conductance voltage (G-V) relationship of Na+

1. at negative voltages conductance is low because channels are most likely closed

2. as voltage increases, conductance increase steeply as the number of channels open increase

3. at positive voltages, conductance levels off a high value because most of the channels are open at that point

(sigmoidal graph)

why does Po change

gated ion channels exhibit changes in Po in response to stimuli

activation

increased activity of a channel in response to a stimulus (ex. for voltage gated channels, and increase in voltage will cause increased activity)

deactivation

reverse of activation, closure of channels and decreased activity when a stimulus is removed but able to reopen again if a stimulus in introduced

what structural change underlie activation and deactivation

1. voltage gated channels are arranged around a central 'pore' that conducts ion (inverted tipi)

2. the central pore has a selective filter region that allows channels to be selective for conducting one type of ion

3. the intracellular side of the pore has a gate

4. the voltage sensing domain undergoes a conformational change in response to changes in membrane voltage to open or close the gate

inactivation

loss of activity in response to an ongoing stimulus (must be recovered and cannot immediately re-open)

what channels exhibit inactivation

all Na+ channels and certain types of K+ channels

when does inactivation set in

at positive voltages

when is inactivation relieved

at negative voltages

what happens to Na+ channels around RMP

they are inactivated and cannot contribute the the firing of an AP

what happens when there are small shifts in RMP

it can impact the number of available Na+ channels and therefore affect excitability

inactivation domains

-each domain has 6 alpha-helical TM segments (S1-S6)

-S1-S4 make up the voltage sensor

-S5-S6 make up the selectivity filter

Na+ inactivation domain

the DIII-IV linker in Na+ channels contains an inactivation domain

what happens if an inactivation domain has a mutation

results in weakened inactivation (eg. IFM mutation, Catterall team)

voltage clamp

when voltage is being controlled by the experimenter and they are measuring the currents passing through

what is the application of using a voltage clamp

how different voltages affects function of an ion channel, or how voltage affects interactions between a ion channel and a blocker

what are voltage clamps most useful for determining

specific details related to ion channel function or drug block (rates of opening, rates of block, voltage dependence opening/block)

current clamp

a constant current pulse is applied designed to excite the cell and to measure the characteristics of APs that follow

what are current clamps useful for

to follow the changes in membrane voltage that occurs during an AP