CJH332H1 Lecture Notes - Lecture 5: Voltage-Gated Potassium Channel, Voltage Clamp, Resting Potential

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25 May 2018
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Lecture 5: The Cellular Dissection (Resting Vs. Action Potentials)
Action Potentials
Hodgkin-Huxley model of the Action Potential and how they were able to figure this out
Re-visiting leak channels and voltage-gated (voltage-dependent) channels
Basic review of the action potential and the movement of ions
What causes the refractory period
Structure-function of voltage-dependent ion channels
Mental health models
Resting membrane potential mainly K+
In 1902, Bernstein postulated that the membrane potential
(Vm) was essentially due to potassium equilibrium potential
There is always high concentration of K+ inside than outside
Changing extracellular concentration of K+ - by increasing it,
he was able to depolarize the membrane (450mM = membrane potential to 0)
He tested his hypothesis by varying the concentration of potassium in the bath and found predictable changes in
the equilibrium potential and that in turn regulated the membrane potential
Not the case for Na+ i erae, e do’t hae uh Na leak channels not much difference)
Background to Action Potentials
AP is an explosive change in electrical activity (sudden change in membrane potential)
APs are transported along an excitable cell such as a nerve or muscle cell
An AP induced by a stimulus
- Electrical change, Chemical (taste, drugs, smell, neurotransmitters)
- Mechanical (touch, pressure, sound) , Light (vision, photo-detection)
- Temperature (hot and cold receptors)
Current clamp:
- Control current injected into neuron (can be 0) and measure membrane potential change (keep current
steady)
- i.e. inject positive current into the neuron and watch it fire AP
Voltage clamp:
- Cotrol euro’s membrane potential and measure the currents that flow across its membrane
- i.e. step the neuron to a depolarized potential and measure voltage-gated currents (keep membrane
potential steady)
Membrane responses part 1
If we use current-clamp mode to observe what happens with the membrane
potential, inject current (hyperpolarizing currents)
Measure what is the change in the membrane potential? it hyperpolarizes
Linear relationship of V = IR
- Bigger current, bigger membrane potential change
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Membrane responses part 2
Inject a positive current positive deflection
Current-clamp mode (current is held steady, measure change in voltage)
Also a linear relationship (all due to leak channels)
Slow steady increase
Explain this using linear relationships?
Keep repeating the steps, there is a massive change in the membrane potential
Passing the threshold value, action potential occurs the same size!
Action Potential general properties
APs results from sudden, large increases in Na+ permeability
This is a voltage gated channel (Na+ and K+)
- Rise and falling phase due to changes in different voltage gated channels open/close
Chagig extraellular Na+ oetratio is’t goig to allo AP ut Na+ is ioled i proess easure peak
Driving force (equilibrium potential for Na) is close to peak of AP
Increases in + charge on the inner surface of the membrane drives Vm towards ENa rising phase of the AP
Cell resting at -65mV will reach above +40mV at peak of the AP
Driving force
We are always interested in the difference between resting membrane potential and equilibrium potential for
any particular ion
- At rest, resting membrane potential is due to changes in permeability in K+ while AP is due to Na+
Threshold for generating an AP
The threshold is the critical value of Vm at which an AP impulse is generated
Threshold is the point at which iNa+ = -iK+ (flow of sodium equal to flow of potassium in opposite direction/out)
As soon as iNa+ exceeds -iK+ (threshold), positive feedback sets in, and an action potential is initiated
Action Potential
When threshold is reached, we can now start
opening voltage gated channels
Falling phase of the AP is also called
repolarization
Repolarization results from a large increase in K+
permeability and loss of + charge on the inner
surface of the membrane
Vm returns towards EK
Ionic basis of Action Potential
Ion channels underlying AP generation are
voltage-dependent
Depolarization increases the membrane conductance to Na+ initially and to K+ after a delay
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Document Summary

Lecture 5: the cellular dissection (resting vs. action potentials) Background to action potentials: ap is an explosive change in electrical activity (sudden change in membrane potential, aps are transported along an excitable cell such as a nerve or muscle cell, an ap induced by a stimulus. Mechanical (touch, pressure, sound) , light (vision, photo-detection) Temperature (hot and cold receptors: current clamp: Control current injected into neuron (can be 0) and measure membrane potential change (keep current steady) i. e. inject positive current into the neuron and watch it fire ap: voltage clamp: Co(cid:374)trol (cid:374)euro(cid:374)"s membrane potential and measure the currents that flow across its membrane i. e. step the neuron to a depolarized potential and measure voltage-gated currents (keep membrane potential steady) Inject a positive current positive deflection: current-clamp mode (current is held steady, measure change in voltage, also a linear relationship (all due to leak channels, slow steady increase.

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