diversity of form and function of voltage- gated potassium channels
DESCRIPTION
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. K Ca 3. K IR. 3 Gene SubFamilies: 6TM 2 TM 4TM Evolutionary tree does not - PowerPoint PPT PresentationTRANSCRIPT
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
3 Gene SubFamilies:6TM2 TM4TM
Evolutionary tree does notcluster by architecture and architectures do not align to specific function.
IK vs. IA: Function can be separated not only pharmacologically, but physiologically by Vh. The formerdrives repolarization while the later spaces successiveAP more widely. Each act to dampen excitability.
3 types of KCa:BK, Maxi KIK, fast AHPSK, slow AHP
Why are state kineticdiagrams so complexfor this type of calcium-activated channel?
Spike FrequencyAdaptation =
Membranes may hyperpolarize twiceand different KCa
channels drive the slow and fast component.
Called = Phasic FiringPatterns
Cl Channels are currently classified according to the activating stimulus to gate the channel, rather than by molecular structure
Fatt and Collaborators:
First discovery of theCalcium Action Potential
What is a CalciumSpike?
Calcium Shapes theRegenerative A.P.
And is in EVERY excitable cell.
Internal Calcium: Three Best Studied Roles =
1. Contraction of Muscle2. Secretion3. Gating
Why is calciumsaid to be TheIon?
How does it act to be A Second Messenger?
Calcium-dependent Exocytosis - Neurotransmittersand Digestive Enzymes
Probability of NTrelease is proportionalto [Ca]3.9
2 Sources of Calcium:1. PM Ca Channels2. Intracellular
Storing Organelles
100s of Docking Associated Proteins!
Resting Calcium ConcentrationIn most cells:
30 – 200 nM
Increases in calcium measuredwith fluorescent Caindicators = small rise and slow fall…..
Is this what physiologicallyoccurs?
A. 1970s Llinas = HVA and LVAB. 1988 Tsien = T and L typeC. 1990s Pharmacology = P/Q, N, and R typeD. 2000 Molecular = Structural Architecture
Therefore the nominclature following molecular era is stilla mix of phenomenological and cloning classification!