Inactivation and Action Potential Kinetics
Trent
Contents
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Inactivation vs. deactivation
Types of inactivation
Effects of inactivation on action potentials
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
Inactivation and deactivation
are both closings of the channel
Deactivation ~ “closed”
closing once the stimulus is removed
Inactivation ~ “not open”
closing while the stimulus is still present
+
Shaker K Channel
N-type inactivation - “ball and chain”
• Faster
• Ball physically blocks pore
• Each subunits contribution is independent
• four balls present, but only one needed
C-type inactivation - “foot in the door”
• Slower
• Conformational change
• cooperative change of all four subunits
Different Processes
closed
Different Domains
open
N-type inactivation
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 neuron
Outside:
[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)
References
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 voltagegated 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