April 21, 2016
PBIO seminar – Claudia Moreno
Couple, amplify, fire!
Coupling of L-type calcium channels and excitability
L-type CaV1.2 and CaV1.3 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 CaV1.2 and CaV1.3 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 CaV1.2 and CaV1.3 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 CaV1.2 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