April 21, 2016

PBIO seminar – Claudia Moreno

Couple, amplify, fire!

Coupling of L-type calcium channels and excitability

L-type Ca_V1.2 and Ca_V1.3 calcium channels are key players in the generation and regulation of electrical activity in different cell types, including neurons and myocytes. In the pacemaker cells of the heart, the spike of the action potential that initiates each heartbeat depends entirely on the entry of calcium through these channels. Recently, we discovered a novel cooperative gating mechanism, on both Ca_V1.2 and Ca_V1.3 channels, which facilitates calcium entry and modulates the excitability of ventricular cardiomyocytes and neurons. We found that these channels establish a calcium-dependent physical interaction via their c-termini, which results in an increase in their open probability. Our more recent project aims to answer two new questions: Do Ca_V1.2 and Ca_V1.3 channel undergo functional coupling in the pacemaking cells of the heart? And, if so, is this coupling modulated by physiological stimuli? Our new results point to a mechanism by which beta-adrenergic signaling increases the coupling of Ca_V1.2 channels in the pacemaker cells. These exciting results add to our understanding on how the sympathetic nervous system increases heart rate.   Claudia Moreno, Ph.D. Department of Physiology and Membrane Biology School of Medicine University of California, Davis host: Stan Froehner