Use of transgenic mice to study voltage-dependent Ca2+ channels

During the past decade a great number of genes encoding high- and low-voItage-dependent Ca2+ channels and their accessory subunits have been cloned. Studies of Ca2+ channel structure-function relationships and channel regulation using cDNA expression in heterologous expression systems have revealed intricate details of subunit interaction, regulation of channels by protein kinase A (PKA) and protein kinase C (PKC), drug binding sites, mechanisms of drug action, the ion conduction pathway and other aspects of channel function. In recent years, however, we have arrived at the brink of an entirely new strategy to study Ca2+ channels by overexpressing or knocking out genes encoding these channels in transgenic mice. In this article, various models of gene knockout or gene overexpression will be discussed. This new approach will reveal many secrets regarding Ca2+ channel regulation and the control of Ca2+-dependent cellular processes.