Regulation of voltage-dependent Ca²⁺ channels in the early developing heart: role of β1 integrins

Abstract

In contrast to adult ventricular cardiomyocytes the developmentally early stage cardiomyocytes show a suppression of the basal voltage-dependent calcium channels (DCC L-type Ca²⁺ channels, I_Ca) by carbachol (CCh). This effect is mediated by the endothelial NO-synthase (NOS III). In contrast late stage and adult cardiomyocytes a direct coupling of the muscarinic receptor to the adenylyl cyclase. Thus, NO may function as an early signal transduction molecule during development. This review elucidates the role of β1-integrins in mediating signal transduction between muscarinic receptors and coupled downstream target proteins such as ion channels. The key finding is that in embryonic stem cell-derived cardiomyocytes deficient of β1-integrins, the modulation of L-type Ca²⁺ channels via the M2 receptor is absent. Experiments indicate that this selective signaling defect occurs at the G-protein level. This suggests a novel critical role for integrins in membrane delimited signal transduction processes.