CBAC Seminar Series Videos
 
Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response: From Molecular Mechanisms to Heart Failure

Title

Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response: From Molecular Mechanisms to Heart Failure

Files

Link to Full Video

Stream Seminar Video

Date

Fall 11-21-2016

Document Type

Seminar Series

Abstract

Intracellular calcium transients generated by activation of voltage-gated calcium (CaV) channels generate local signals, which initiate physiological processes such as secretion, synaptic transmission, and excitation-contraction coupling. Regulation of calcium entry through CaV channels is crucial for control of these physiological processes. In this article, I review experimental results that have emerged over several years showing that cardiac CaV1.2 channels form a local signaling complex, in which their proteolytically processed distal C-terminal domain, an A-Kinase Anchoring Protein, and cyclic AMP-dependent protein kinase (PKA) interact directly with the transmembrane core of the ion channel through the proximal C-terminal domain. This signaling complex is the substrate for β-adrenergic up-regulation of the CaV1.2 channel in the heart during the fight-or-flight response. Protein phosphorylation of two sites at the interface between the distal and proximal C-terminal domains contributes importantly to control of basal CaV1.2 channel activity, and phosphorylation of Ser1700 by PKA at that interface up-regulates CaV1.2 activity in response to β-adrenergic signaling. Thus, the intracellular C-terminal domain of CaV1.2 channels serves as a signaling platform, mediating beat-to-beat physiological regulation of channel activity and up-regulation by β-adrenergic signaling in the fight-or-flight response.

Biography

Chair & Professor, Department of Pharmacology, University of Washington

Research/Clinical Interests

http://depts.washington.edu/phcol/faculty/catterall.php

Publications

https://www.ncbi.nlm.nih.gov/pubmed?cmd=Search&term=Catterall%20WA[Auth]

Flyer

https://wustl.box.com/s/6mcywn5b48fjpdjk73pyz5jiogeih8e4

Regulation of Cardiac Calcium Channels in the Fight-or-Flight Response: From Molecular Mechanisms to Heart Failure

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