Beta Subunit Regulation of Voltage-Gated Ca Channels

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DESCRIPTION (provided by applicant): The importance of calcium as the trigger for exocytosis has been well established making modulation of the kinetics of voltage-gated Ca channels one method through which neurons can exert regulatory control over synaptic efficacy. Ca channel beta-subunits have a strong influence over the activation, inactivation and steady-state inactivation of these channels and therefore could potentially serve as a mechanism through which alteration of Ca channel kinetics could be accomplished. This proposal is focused on testing the hypothesis that beta-subunits regulate the degree of calcium current depression produced by high frequency trains of action potentials by shifting the steady-state inactivation profiles of voltage-gated Ca channels. Beta-subunit specific modulation of cloned calcium channels will initially be examined in tsA2Ol cells and subsequently in superior cervical ganglion neurons to assess the basic characteristics and physiological significance of this proposed mechanism which may in part regulate synaptic plasticity.