Regulation of voltage-dependent Ca2+ channels in the early developing heart: role of beta1 integrins.
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 beta1-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 beta1-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.
Hescheler
Jürgen
J
Institut für Neurophysiologie, Universität zu Köln, Robert-Koch-Str. 39, 50931 Köln, Germany. J.Hescheler@uni-koeln.de
Fleischmann
Bernd K
BK
D000818:Animals; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type / Q000378:metabolism; D004622:Embryo, Mammalian / Q000378:metabolism / Q000502:physiology; D004625:Embryo, Nonmammalian; D006321:Heart / Q000196:embryology*; D019012:Integrin beta1 / Q000502:physiology*; D009569:Nitric Oxide / Q000502:physiology
D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D019012:Integrin beta1; D009569:Nitric Oxide