Ion Channels & Cellular Electrophysiology

Ion Channels & Cellular Electrophysiology
Mark Beenhakker membrane voltage cell electrical signals action potential pumps & channels

A Three-Hour Lecture with Three Parts

Mark Beenhakker membrane voltage cell electrical signals action potential pumps & channels

Pumps & Channels inside outside membrane pump channel

Pumps & Channels x outside membrane inside pump channel

Pumps & Channels passive transport active transport x x x x pump
outside membrane inside pump channel passive transport active transport

Pumps & Channels active transport ATP x pump channel outside membrane
inside pump channel ATP active transport

Pumps & Channels active transport ATP x pump channel outside membrane
inside pump channel active transport

Pumps & Channels active transport ADP ATP x x pump channel outside
membrane ATP inside pump channel P P active transport

Pumps & Channels ATP ATP-Driven Pumps Na+-K+ Pump x pump channel
outside membrane ATP inside pump channel P P P-type pumps ABC transporters V-type pumps ATP-Driven Pumps Na+-K+ Pump

Pumps & Channels Na+-K+ Pump pump channel outside membrane inside ATP

Pumps & Channels Na+-K+ Pump Na+-K+ Pump pump channel pump channel
outside outside membrane membrane pump channel inside inside pump channel Na+ Na+ Na+ Na+ Na+ Na+ Na+-K+ Pump Na+-K+ Pump

Pumps & Channels pump channel Key Points outside membrane inside
The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

X Pumps & Channels passive movement x x x x pump channel outside
inside outside membrane pump channel passive movement

X Pumps & Channels passive movement x x x x x x when will it end?
equilibrium x x X inside outside membrane pump channel x x x x passive movement

Pumps & Channels + + + + + + + + + + + + + + + + + + + + + + - - - - -
equilibrium + + + + + + + + + + + + + + + + + + + + + + + inside outside membrane pump channel - - - - - - - - - - - - - - - - + passive movement

Pumps & Channels + - + + + + + + + + + + + + + + + passive movement
electrochemical equilibrium + + + inside outside membrane pump channel - + + + + + + + + + + + + + passive movement

Pumps & Channels + + + + + - + + + + + + + Vm - - - - - - - - - + + +
equilibrium electrochemical + + equilibrium potential + + + + + - + + + + + + + Vm inside outside membrane pump channel - - - - - - - - - + + + + + + + + + + + + + passive movement

Pumps & Channels + + Vm - Vm + + + + + + + + + + + + +
equilibrium electrochemical + + + + + + equilibrium potential + + Vm inside outside membrane channel Vm - + + + + + + + “reversal” potential passive movement “Nernst” potential

Pumps & Channels + Nernst Equation + Vequilibrium= ln - Vm + + + + + +
electrochemical + + + equilibrium potential + Vequilibrium= RT zF ln [X] Nernst Equation o i + inside outside membrane channel Vm R = gas constant T = temperature Z = valence of the ion F = Faraday’s constant - + + + + + + + “reversal” potential passive movement “Nernst” potential

Pumps & Channels + Nernst Equation + Vequilibrium= ln - + + + + + + +
electrochemical + + + Vequilibrium= RT zF ln [X] Nernst Equation + inside outside o membrane i channel R = gas constant T = temperature Z = valence of the ion F = Faraday’s constant - + + + + + + + + + + passive movement

Pumps & Channels + Nernst Equation + Vequilibrium = ln - + + + + + + +
electrochemical + + + Nernst Equation + RT zF [X] inside outside Vequilibrium = o ln [X] membrane i channel R = gas constant T = temperature Z = valence of the ion F = Faraday’s constant Key Points - The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. + + + + + + + + When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. + + + + The equilibrium set point of each ionic species is associated with a specific membrane voltage. passive movement Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps & Channels inside outside membrane

ENa EK ECl Pumps & Channels Nernst Equation Vequilibrium = ln RT zF
[X] Nernst Equation o i Na+ K+ Cl- Na+ Cl- inside outside membrane sodium channel potassium channel chloride channel K+ ENa EK ECl

ENa EK ECl Pumps & Channels PNa[Na]o + PK[K]o + PCl[Cl]i RT Vm =
PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i Vm = RT F ln Vequilibrium = RT zF ln [X ] o i Na+ K+ Cl- Cl- inside outside membrane sodium channel potassium channel chloride channel ENa EK ECl

PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i Vm = RT F ln
Pumps & Channels PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i Vm = RT F ln inside outside membrane sodium channel potassium channel chloride channel

Pumps & Channels per·me·a·bil·i·ty: the state or quality of a material
or membrane that causes it to allow liquids or gases to pass through it. inside outside membrane sodium channel potassium channel chloride channel

Pumps & Channels per·me·a·bil·i·ty: the ability of an ion to pass
through the membrane. inside outside membrane sodium channel potassium channel chloride channel

Pumps & Channels PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i Vm = RT F ln inside outside membrane Key Points sodium channel potassium channel chloride channel The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. The equilibrium set point of each ionic species is associated with a specific membrane voltage. The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps & Channels what opens a channel? Key Points outside membrane
inside outside membrane Key Points The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps & Channels what opens a channel? inside outside membrane

Pumps & Channels what gates a channel? inside outside membrane

Pumps & Channels - + + what gates a channel? voltage- gated voltage
inside outside voltage sensor membrane voltage- gated

Pumps & Channels + - + + what gates a channel? ligand- gated voltage-
inside outside voltage sensor membrane -100 -50 -25 -75 voltage (mV) open probability 0.0 0.5 1.0 ligand binding site voltage- gated

Pumps & Channels + - + + what gates a channel? mechanically- gated
sensor + - + + mechanically- gated inside outside voltage sensor membrane ligand binding site voltage- gated ligand- gated

Pumps & Channels + - + + what gates a channel? voltage- gated ligand-
mechanical sensor + - + + inside outside voltage sensor membrane ligand binding site Key Points The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. voltage- gated ligand- gated mechanically- gated The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps & Channels This equation defines the voltage across the membrane (Vm) PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i Vm = RT F ln Key Points The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps & Channels Key Points
The Na+-K+ pump uses ATP to drive Na+ out of — and K+ into — a cell, thereby establishing strong Na+ and K+ gradients across the membrane. When permitted, ionic species want to achieve equilibrium, a state that is defined both chemically and electrically. The equilibrium set point of each ionic species is associated with a specific membrane voltage. Channels are activated by diverse mechanisms. When active, they transiently enable an ion to reach equilibrium. In doing so, channels can change the voltage of a cell.

Pumps ATP-Driven Pumps Na-K Pump Na-K Gradients Channels Equilibrium Potential Ion-Selective Channels Channel Gating

membrane voltage cell electrical signals action potential pumps & channels

Pumps ATP-Driven Pumps Na-K Pump Na-K Gradients Channels Equilibrium Potential Ion-Selective Channels Channel Gating

Na+ K+ Na-K Pump cell

Na+ Membrane Potential Na+ K+ Na+ Na+ Na+ Na+ Na+ Na+ Na+ K+ Na+ RT F PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i ln Potassium Channel Sodium Channel Chloride Channel Na+ Na+ K+ K+ K+ Na+ K+ Na+ K+ K+ Na+ K+ Na+ Na+ Na+ K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ K+ K+ K+ K+ K+ Na+ K+ Na+ Na+ K+ K+ Na+ Na+ K+ K+ K+ K+ Na+ K+ K+ Na+ Na+ K+ K+ K+ K+ K+ K+ Na+ K+ K+ K+ Na+ K+ Na+ K+ K+ K+ Na+ Na+ K+ K+ Na+ K+ Na-K Pump Na+ Na+ Na+ K+ K+ K+ Na+ Na+ K+ Na+ K+ K+ K+ K+ Na+ Na+ Na+ K+ Na+ K+ Na+ cell Na+ Na+ Na+ K+ Na+ Na+ Na+ Na+ K+

Na+ Membrane Potential Na+ K+ Na+ Na+ Na+ Na+ Na+ Na+ RT F PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i ln Potassium Channel Sodium Channel Chloride Channel Na+ Na+ Na+ K+ K+ K+ Na+ K+ Na+ K+ K+ Na+ K+ Na+ Na+ Na+ K+ K+ K+ Na+ K+ K+ K+ Na+ Na+ Na+ K+ K+ Nernst Equation RT zF ln PK[K]i PK[K]o EK = K+ K+ K+ Na+ K+ Na+ Na+ K+ Na+ Na+ K+ K+ K+ K+ K+ Na+ K+ K+ Na+ Na+ K+ K+ K+ K+ K+ K+ EK = -90mV K+ K+ Na+ K+ Na+ K+ Na+ K+ K+ Na+ Na+ K+ K+ K+ ENa = +50mV Na+ K+ Na-K Pump Na+ Na+ Na+ K+ K+ K+ ECl = -70mV Na+ Na+ K+ Na+ K+ K+ K+ K+ Na+ Na+ Na+ K+ Na+ K+ Na+ cell Na+ Na+ Na+ K+ Na+ Na+ Na+ Na+ K+

Na-K Gradients Ion-Selective Channels Membrane Voltage

membrane voltage cell electrical signals action potential pumps & channels

Membrane Potential RT F PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i ln ENa = +50mV EK = -90mV ECl = -70mV cell Na-K Pump Sodium Channel Potassium Channel Chloride Channel

Membrane Potential RT F PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i ln ENa = +50mV EK = -90mV ECl = -70mV cell Na-K Pump Sodium Channel Vm Delayed Rectifier Potassium Channel Potassium Channel (leak) Chloride Channel

Membrane Potential RT F PNa[Na]i + PK[K]i + PCl[Cl]o PNa[Na]o + PK[K]o + PCl[Cl]i ln ENa = +50mV EK = -90mV ECl = -70mV cell Na-K Pump Sodium Channel Vm Delayed Rectifier Potassium Channel Potassium Channel (leak) Chloride Channel action potential

Membrane Potential RT PNa[Na]o + PK[K]o + PCl[Cl]i ln F PNa[Na]i + PK[K]i + PCl[Cl]o ENa = +50mV EK = -90mV ECl = -70mV cell Na-K Pump Sodium Channel Vm Delayed Rectifier Potassium Channel Potassium Channel (leak) Chloride Channel action potential

Membrane Potential RT PNa[Na]o + PK[K]o + PCl[Cl]i ln F PNa[Na]i + PK[K]i + PCl[Cl]o ENa = +50mV EK = -90mV ECl = -70mV cell Na-K Pump Sodium Channel Delayed Rectifier Potassium Channel Potassium Channel (leak) Chloride Channel

Na-K Gradients Ion-Selective Channels Membrane Voltage

Mark Beenhakker electrical signals action potential pumps & channels membrane voltage cell

Ion Channels & Cellular Electrophysiology

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