Calcium: Nodal Regulator of Contractility and Hypertrophy in Cardiac Myocytes

Abstract

This lecture will discuss Calcium (Ca 2+ ) influx pathways involved in the regulation of cardiac contractility and cardiac responses to pathological stress. The lecture will review the data showing that the persistent increases in Ca 2+ influx required for myocytes that have persistently increased contractile demands can induce pathological cardiac myocyte hypertrophy and can induce myocyte death signaling pathways. The respective sources of Ca 2+ that activate contractile proteins (to produce enhanced force development) and hypertrophic or death signaling cascades will be discussed. Recent data suggests that the sources of Ca 2+ for regulation of contractile function and hypertrophy signaling are distinct. L-type Ca 2+ channels (LTCCs) and Transient Receptor Potential (TRP) channels appear to be sources of Ca 2+ for signaling and LTCCs are the primary source of Ca 2+ to activate excitation contraction coupling. The idea that TRP and LTCCs are housed in cellular microdomains to locally activate partner proteins that lead to either contraction or activation of signaling cascades will be discussed. Data to be presented suggests that housing the same molecules, LTCCs and TRP channels, in separate membrane microdomains allows the same class of ion channels to affect either excitation contraction coupling or signaling partners.