CLONING AND EXPRESSION OF A NEURONAL CALCIUM-CHANNEL BETA-SUBUNIT

Although pharmacological and electrophysiological studies have demonst rated the existence of multiple types of voltage-dependent calcium cha nnels in neuronal tissue, the subunit composition of these channels is not well known. Here, we report the cloning and expression of a new r at brain beta subunit (beta4). Northern blot analysis indicates that b eta4 mRNA is expressed almost exclusively in neuronal tissues, with th e highest levels being found in the cerebellum. Coexpression studies i ndicate that rat beta4 can interact with rabbit cardiac muscle alpha1, rabbit skeletal muscle alpha1, and calcium channels endogenous to Xen opus oocytes. Beta4 modulation of alpha1 activity is similar to the mo dulation induced by beta1, beta2, or beta3. The most striking effect o f beta subunits is their ability to increase functional alpha1 activit y, which can be measured as either increased dihydropyridine binding t o membranes from transfected COS cells or increased calcium channel ac tivity in Xenopus oocytes.