Ion Channels amp Cellular Electrophysiology Mark Beenhakker markbeenvirginiaedu electrical signals action potential pumps amp channels membrane voltage cell membrane Pumps amp Channels ID: 930592
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Slide1
Slide2CCIB
The Seventh Block
http://beenhakkerlab.org/
Slide3Ion Channels & Cellular Electrophysiology
Mark Beenhakker
markbeen@virginia.edu
electrical
signals
action potential
pumps &
channels
membrane
voltage
cell
Slide4membrane
Pumps & Channels
channel
pump
inside
outside
Slide5membrane
channel
pump
x
inside
outside
Pumps & Channels
Slide6membrane
channel
pump
inside
outside
x
Pumps & Channels
Slide7membrane
channel
inside
outside
x
pump
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
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x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
passive transport
active transport
Pumps & Channels
Slide8membrane
channel
inside
outside
x
pump
active transport
ATP
Pumps & Channels
Slide9membrane
channel
inside
outside
pump
active transport
x
ATP
Pumps & Channels
Slide10membrane
channel
inside
outside
pump
active transport
x
P
P
ATP
ADP
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
Pumps & Channels
Slide11membrane
channel
inside
outside
pump
P-type pumps
ABC transporters
V-type pumps
ATP-Driven Pumps
Na
+
-K
+
Pump
x
P
P
ATP
Pumps & Channels
Slide12membrane
channel
inside
outside
pump
Na
+
K
+
K
+
Na
+
Na
+
Na
+
-K
+
Pump
ATP
P
Pumps & Channels
Slide13membrane
channel
inside
outside
pump
Na
+
-K
+
Pump
K
+
K
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
membrane
channel
inside
outside
pump
Na
+
-K
+
Pump
K
+
K
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
K
+
K
+
K
+
Pumps & Channels
Slide14membrane
pump
inside
outside
channel
Pumps & Channels
Slide15membrane
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
xxxxxchannelpump
inside
outside
passive movement
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
X
Pumps & Channels
Slide16membrane
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
x
xxxxxx
channelpump
inside
outside
passive movement
when will it end?
equilibrium
x
x
x
x
x
x
x
x
x
X
Pumps & Channels
Slide17+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
membrane
channelpump
inside
outside
passive movement
equilibrium
+
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
Pumps & Channels
Slide18+
membrane
+
+
+
+
+
+
+
+
channel
pump
inside
outside
passive movement
equilibrium
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
-
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
electrochemical
Pumps & Channels
Slide19Vm
+
+
membrane
pump
-
-
-
-
-
-
-
+
+
+
+
+
+
++
-
+
-
+
+
+
+
+
+
+
+
channel
inside
outside
passive movement
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
+
-
-
-
-
-
-
-
+
+
+
+
+
+
+
+
+
+
+
equilibrium
potential
+
Pumps & Channels
equilibrium
electrochemical
Slide20Vm
membrane
+
+
+
+
+
+
channel
inside
outside
passive movement
+
+
+
+
+
+
+
++-------+++++++++
+
++
equilibrium
potential
Vm
+
+
+
“reversal” potential
“Nernst” potential
+
Pumps & Channels
equilibrium
electrochemical
Slide21+
+
+
+
Vm
membrane
+
+
channel
inside
outside
passive movement
+
+
+
+
+
+
+
++-------+++++++++++
equilibrium
potential
“reversal” potential“Nernst” potential
R = gas constant
T = temperature
Z = valence of the ion
F = Faraday’s constant
V
equilibrium
=
RT
zF
ln
[X]
[X]
Nernst Equation
o
i
+
Pumps & Channels
equilibrium
electrochemical
Slide22V
equilibrium
=
RT
zF
ln
[X]
[X]
Nernst Equation
+
+
membrane
+
+
channel
inside
outside
passive movement
+++++
++++++-------+++++++++++
+
+
++
+
+
+
+
o
i
+
Pumps & Channels
equilibrium
electrochemical
R = gas constant
T = temperature
Z = valence of the ion
F = Faraday’s constant
Slide23+
+
+
V
equilibrium
RT
zF
ln
[X]
[X]
Nernst Equation
+
membrane
+
+
channel
inside
outside
passive movement+++
++++-------+++++++++++
+
++
+++
+
+
+
+
+
+
=
o
i
+
Pumps & Channels
equilibrium
electrochemical
R = gas constant
T = temperature
Z = valence of the ion
F = Faraday’s constant
Slide24membrane
inside
outside
Pumps & Channels
Slide25membrane
inside
outside
Na
+
K
+
Cl
-
sodium
channel
potassium
channel
chloride
channel
Na
+
Na
+
Na
+
Na
+Na+
Na
+
K
+
K
+
K
+
K
+
K
+
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
E
Na
E
K
E
Cl
V
equilibrium
=
RT
zF
ln
[X]
[X]
Nernst Equation
o
i
Pumps & Channels
Slide26membrane
inside
outside
Cl
-
sodium
channel
potassium
channel
chloride
channel
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+K+
K
+
K
+
K
+
K
+
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
Cl
-
E
Na
E
K
E
Cl
V
equilibrium
=
RT
zF
ln
[X ]
[X ]
o
i
P
Na
[Na]
i
+ P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+ P
K
[K]
o
+
P
Cl
[Cl]
i
V
m
=
RT
F
ln
Pumps & Channels
Slide27P
Na
[Na]
i
+
P
K
[K]
i
+ PCl[Cl]oPNa[Na]o + PK[K]o + PCl[Cl]i
Vm
=
RT
F
ln
membraneinsideoutsidesodiumchannelpotassiumchannel
chloridechannel
Pumps & Channels
Slide28membrane
inside
outside
sodium
channel
potassium
channel
chloride
channel
per·me·a·bil·i·ty
:
the state or quality of a material or membrane that causes it to allow liquid or gases to pass through it.
Pumps & Channels
Slide29membrane
inside
outside
sodium
channel
potassium
channel
chloride
channel
through the membrane.
per·me·a·bil·i·ty
:
the ability of an ion to pass
Pumps & Channels
Slide30P
Na
[Na]
i
+
P
K
[K]
i
+ PCl[Cl]oPNa[Na]o + PK[K]o + PCl[Cl]i
Vm
=
RT
F
ln
membraneinsideoutsidesodiumchannelpotassiumchannel
chloridechannel
Pumps & Channels
Slide31membrane
inside
outside
sodium
channel
potassium
channel
chloride
channel
what opens a channel?
Pumps & Channels
Slide32membrane
inside
outside
what opens a channel?
Pumps & Channels
Slide33membrane
inside
outside
what
gates
a channel?
Pumps & Channels
Slide34membrane
inside
outside
voltage-
gated
what
gates
a channel?
+
+
+
+
+
+
+
+
+
+
+++-------voltagesensorPumps & Channels
Slide35+
+
+
+
+
+
+
-
-
-
-
---membraneinsideoutside
voltage-
gated
what
gates
a channel?
+
+++++voltagesensor
ligand-gatedligandbindingsite
-100
-50
-25
0
-75
voltage (mV)
open probability
0.0
0.5
1.0
Pumps & Channels
Slide36+
+
+
+
+
+
+
-
-
-
-
---membraneinsideoutside
voltage-
gated
what
gates
a channel?
+
+++++voltagesensorligand-
gatedligandbindingsite
mechanically-
gated
mechanical
sensor
Pumps & Channels
Slide37+
+
+
+
+
+
+
-
-
-
-
---membraneinsideoutside
voltage-
gated
what
gates
a channel?
+
+++++voltagesensorligand-
gatedligandbindingsite
mechanically-
gated
mechanical
sensor
Pumps & Channels
Slide38P
Na
[Na]
i
+
P
K
[K]
i
+ PCl[Cl]oPNa[Na]o + PK[K]o + PCl[Cl]i
Vm
=
RT
F
ln
membraneinsideoutsidesodiumchannelpotassiumchannel
chloridechannel
Pumps & Channels
Slide39Pumps
ATP-Driven Pumps
Na-K Pump
Na-K Gradients
Channels
Equilibrium Potential
Ion-Selective Channels
Channel Gating
Ion Channels & Cellular Electrophysiology
Slide40electrical
signals
action potential
pumps &
channels
membrane
voltage
cell
Ion Channels & Cellular Electrophysiology
Slide41pumps &
channels
membrane
voltage
cell
electrical
signals
action potential
Ion Channels & Cellular Electrophysiology
Slide42Pumps
ATP-Driven Pumps
Na-K Pump
Na-K Gradients
Channels
Equilibrium Potential
Ion-Selective Channels
Channel Gating
Ion Channels & Cellular Electrophysiology
Slide43cell
Na-K Pump
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K+K+K+K+K+K+K+K+K+K+K+K+
K+K+K+K+K+K+K+K+K+K+K+K+
K
+K+K+
K+K+K+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Ion Channels & Cellular Electrophysiology
Slide44Potassium Channel
Sodium Channel
Chloride Channel
cell
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K+K+K+K+K+K+K+K+K+
K+K+K+K+K+K+K+K+K+K+K+K+
K
+K+K+
K+K+K+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na-K Pump
RT
F
P
Na
[Na]
i
+ P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+ P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
Ion Channels & Cellular Electrophysiology
Slide45Potassium Channel
Sodium Channel
Chloride Channel
cell
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K+K+K+K+K+K+K+K+K+
K+K+K+K+K+K+K+K+K+K+K+K+
K
+K+K+
K+K+K+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
K
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na
+
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
Nernst Equation
RT
zF
ln
P
K
[K]
i
P
K
[K]
o
E
K
=
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Ion Channels & Cellular Electrophysiology
Slide46Na-K Gradients
Ion-Selective Channels
Membrane Voltage
Ion Channels & Cellular Electrophysiology
Slide47pumps &
channels
membrane
voltage
cell
electrical
signals
action potential
Ion Channels & Cellular Electrophysiology
Slide48membrane
voltage
cell
pumps &
channels
electrical
signals
action potential
Ion Channels & Cellular Electrophysiology
Slide49Potassium Channel
Chloride Channel
cell
Sodium Channel
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Ion Channels & Cellular Electrophysiology
Slide50Potassium Channel (leak)
Chloride Channel
cell
Sodium Channel
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Delayed Rectifier
Potassium Channel
Vm
Ion Channels & Cellular Electrophysiology
Slide51cell
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Vm
Potassium Channel (leak)
Chloride Channel
Sodium Channel
Delayed Rectifier
Potassium Channel
Ion Channels & Cellular Electrophysiology
Slide52cell
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Vm
Potassium Channel (leak)
Chloride Channel
Sodium Channel
Delayed Rectifier
Potassium Channel
action potential
Ion Channels & Cellular Electrophysiology
Slide53cell
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Vm
Potassium Channel (leak)
Chloride Channel
Sodium Channel
Delayed Rectifier
Potassium Channel
action potential
Ion Channels & Cellular Electrophysiology
Slide54cell
Na-K Pump
RT
F
P
Na
[Na]
i
+
P
K
[K]
i
+
P
Cl
[Cl]
o
P
Na
[Na]
o
+
P
K
[K]
o
+
P
Cl
[Cl]
i
ln
Membrane Potential
E
K
= -90mV
E
Na
= +50mV
E
Cl
= -70mV
Potassium Channel (leak)
Chloride Channel
Sodium Channel
Delayed Rectifier
Potassium Channel
Ion Channels & Cellular Electrophysiology
Slide55Na-K Gradients
Ion-Selective Channels
Membrane Voltage
Ion Channels & Cellular Electrophysiology
Slide56Mark Beenhakker
markbeen@virginia.edu
electrical
signals
action potential
pumps &
channels
membrane
voltage
cell
Ion Channels & Cellular Electrophysiology