Inactivation and Action Potential Kinetics

Trent

• Inactivation vs. deactivation• Types of inactivation• Effects of inactivation on action potentials

Contents

Disclaimer

Like all proteins, there is a great deal of variety within as well as between classes. I will try to distinguish between properties that are specific to a channel and trends that may be generalized.

Tentative answers: KcsA

Deactivation ~ “closed”closing once the stimulus is removed

Inactivation ~ “not open”closing while the stimulus is still present

Inactivation and deactivationare both closings of the channel

N-type inactivation - “ball and chain”• Faster• Ball physically blocks pore• Each subunits contribution is independent

• four balls present, but only one needed

Shaker K Channel+

C-type inactivation - “foot in the door”• Slower• Conformational change

• cooperative change of all four subunits

Different Processes Different Domains

N-type inactivation

closed open inactivated

C type inactivation model

Inactivation diversity

P-type inactivation - • Conformational changes in the pore• may be a medium component distinct from C-type

• can be considered c-type, because c-type is a broad category

U-type inactivation - • Unusual voltage dependence of inactivation• Example of the complexity of all these mechanisms

Dr. Saxena’s Question

1. What ion channels are responsible for the depolarization and hyperpolarization in action potentials?

2. What is the effect of the following types of inactivation:• Faster Na+ channel inactivation• Slower Na+ channel inactivation• Faster K+ channel inactivation• Slower K+ channel inactivation

Canonical neuronOutside:

[Na+][K+]

Inside:[Na+][K+]

Copyright (1997):Mike E. McCourt,

NDSU

What are we looking for?

1. Relative rates of:• depolarization (Na+ influx)• hyperpolarization (K+ efflux)

2. Amplitude of:• action potential peak• after hyperpolarization (AHP)

Choc, Senyon, 2002. Potassium channel structures. Nature Reviews Neuroscience; Nature Reviews Neuroscience 3, 115-121.

Kurata, H.T., Fedida, D., 2006. A structural interpretation of voltage-gated potassium channel inactivation. Progress in Biophysics & Molecular Biology; Vol. 92 Issue 2, p185-208.

McCourt, Mike E. Department of Psychology, North Dakota State University. http://www.psych.ndsu.nodak.edu/mccourt/Psy460/Neurophysiology%20of%20vision/Neurophysiology%20of%20vision.html

References