SENSITIZATION OF INSP(3)-DEPENDENT CALCIUM SIGNALING THROUGH STRUCTURAL MODIFICATION OF VOLTAGE-DEPENDENT CALCIUM-CHANNEL - A PHYSIOLOGICALRELEVANCE OF THE CALCIUM-CHANNEL BETA-SUBUNIT

The expression in Xenopus oocytes of the human voltage-dependent Ca2channel (VDCC) beta(2) Subunit subtype (h beta(2)) enhances the endoge nous Ca2+ channel activity. By using the native Ca2+-dependent chlorid e conductance to monitor fast intracellular Ca2+ variations, we point out that the beta-enhanced Ca2+ entry (T-1 component) is currently ass ociated with a second delayed elevation of internal Ca2+ (T-2 componen t). Further experiments show that this additional component absolutely requires Ca2+ entry through the beta-modulated channels although it d irectly derives from a Ca2+ release from intracellular inositol (1,4,5 )-trisphosphate (InsP(3))-sensitive stores. Finally, our study demonst rates that InsP(3)-evoked response in oocytes is dramatically modified since it gains a new shape of voltage dependency directly derived fro m the beta-modified Ca2+ influx. The main conclusion is that the spati otemporal pattern of InsP(3)-dependent Ca2+ release may be closely inf luenced by the intrinsic characteristics of working VDCCs. (C) 1995 Ac ademic Press, Inc.