Diversity of Form and

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Diversity of Form and Function of Voltage- Gated
Potassium Channels
80 Family Members 5 Architectures 3 Gene
SubFamilies
Classes to highlight function 1. Shaker
2. KCa 3. KIR
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3 Gene SubFamilies 6TM 2 TM 4TM Evolutionary
tree does not cluster by architecture and
architectures do not align to specific function.
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Frequency-modulated code The stronger the
injected current, the higher the rate of AP
frequency
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IK vs. IA Function can be separated not only
pharmacologically, but physiologically by Vh.
The former drives repolarization while the later
spaces successive AP more widely. Each act to
dampen excitability.
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3 types of KCa BK, Maxi K IK, fast AHP SK, slow
AHP
Why are state kinetic diagrams so complex for
this type of calcium-activated channel?
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Spike Frequency Adaptation Membranes may
hyperpolarize twice and different KCa channels
drive the slow and fast component. Called
Phasic Firing Patterns
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Bursting Pacemaker Electrical Activity
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KIR The anomalous rectifiers
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Ih can increase cardiac pacemaker activity
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Cl Channels are currently classified according to
the activating stimulus to gate the channel,
rather than by molecular structure
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Fatt and Collaborators First discovery of
the Calcium Action Potential What is a
Calcium Spike? Calcium Shapes the Regenerative
A.P. And is in EVERY excitable cell.
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• Internal Calcium Three Best Studied Roles
• Contraction of Muscle
• Secretion
• Gating

Why is calcium said to be The Ion? How does it
act to be A Second Messenger?
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Calcium-dependent Exocytosis -
Neurotransmitters and Digestive Enzymes

• Probability of NT
• release is proportional
• to Ca3.9
• 2 Sources of Calcium
• PM Ca Channels
• Intracellular
• Storing Organelles
• 100s of Docking
• Associated Proteins!

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Resting Calcium Concentration In most cells 30
200 nM Increases in calcium measured with
fluorescent Ca indicators small rise and slow
fall.. Is this what physiologically occurs?
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1. 1970s Llinas HVA and LVA
2. 1988 Tsien T and L type
3. 1990s Pharmacology P/Q, N, and R type
4. 2000 Molecular Structural Architecture

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Therefore the nominclature following molecular
era is still a mix of phenomenological and
cloning classification!
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Physiological time course of Inactivation of
calcium channels is likely much shorter
than biophysical experiments.. Due to high
use of barium to visualize the small currents.
2 Pulse To allow the internal Ca entry and then
measure fraction of Ca channels that are
inactivated.