1. Diversity of Form and
Function of Voltage-
Gated Potassium Channels
80 Family Members
5 Architectures
3 Gene SubFamilies
Classes to highlight function:
1. Shaker KCa KIR

2. 3 Gene SubFamilies:
6TM
2 TM
4TM
Evolutionary tree does not
cluster by architecture
and architectures do not
align to specific function.

3. Frequency-modulated code =
The stronger the injected current, the higher the
rate of AP frequency

4. 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.

5. 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?

6. Spike Frequency
Adaptation =
Membranes may
hyperpolarize twice
and different KCa
channels drive the
slow and fast
component.
Called = Phasic Firing
Patterns

7. Bursting Pacemaker Electrical Activity

8. KIR: The anomalous rectifiers

9. Ih can increase cardiac pacemaker activity

10. Cl Channels are currently classified according to the
activating stimulus to gate the channel, rather than
by molecular structure

11. 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.

12. 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?

13. Calcium-dependent Exocytosis - Neurotransmitters
and Digestive Enzymes
Probability of NT
release is proportional
to [Ca]3.9
2 Sources of Calcium:
PM Ca Channels
Intracellular
Storing Organelles
100s of Docking
Associated Proteins!

14. 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?

15. 1970s Llinas = HVA and LVA
1988 Tsien = T and L type
1990s Pharmacology = P/Q, N, and R type
2000 Molecular = Structural Architecture

16. Therefore the nominclature following molecular era is still
a mix of phenomenological and cloning classification!

17. 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.