PUB - Publikationen an der Universität Bielefeld

The L-type Ca_v1.2 calcium channel is present throughout the animal kingdom and is essential for some aspects of CNS function, cardiac and smooth muscle contractility, neuroendocrine regulation, and multiple other processes. The L-type Ca_V1.2 channel is built by up to four subunits; all subunits exist in various splice variants that potentially affect the biophysical and biological functions of the channel. Many of the Ca_V1.2 channel properties have been analyzed in heterologous expression systems including regulation of the L-type Ca_V1.2 channel by Ca²⁺itself and protein kinases. However, targeted mutations of the calcium channel genes confirmed only some of these in vitro findings. Substitution of the respective serines by alanine showed that β-adrenergic upregulation of the cardiac Ca_V1.2 channel did not depend on the phosphorylation of the in vitro specified amino acids. Moreover, well-established in vitro phosphorylation sites of the Ca_Vβ₂subunit of the cardiac L-type Ca_V1.2 channel were found to be irrelevant for the in vivo regulation of the channel. However, the molecular basis of some kinetic properties, such as Ca²⁺-dependent inactivation and facilitation, has been approved by in vivo mutagenesis of the Ca_V1.2α₁gene. This article summarizes recent findings on the in vivo relevance of well-established in vitro results.