description): The goal of this proposal is to refine the understanding of the function and molecular pharmacology of T-type Ca channels. The experimental approach utilizes the patch clamp technique to study the biophysics and second messenger modulation of the first two cloned T-type Ca channels, alpha1H and alpha1G, heterologously expressed in HEK 2993 cells. There are four specific aims.
Specific aim 1 identifies the metabolites of arachidonic acid (AA) metabolism that mediate blockade of T-type Ca channels.
Specific aim 2 evaluates the contribution of PKC/G protein modulation of T-type Ca channels.
Specific aim 3 defines the molecular transitions that underlie isoform-specific current kinetics and access the mechanism of channel modulation.
Specific aim 4 proposes to identify the sites of the interaction between second messengers and T-type Ca channels.
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