RELATIVE CONTRIBUTIONS OF G-PROTEIN, CHANNEL, AND RECEPTOR TO VOLTAGE-DEPENDENT INHIBITION OF NEURONAL N-TYPE AND P Q-TYPE CALCIUM CHANNELSIN HEK-293 CELL-LINES/

The voltage-dependent modulation of neuronal voltage-gated calcium cha nnels by heterotrimeric G protein-coupled receptors potentially provid es a means for activity-dependent modulation of synaptic efficacy. Rec ent attention has focused upon the molecular mechanisms by which such G proteins influence the biophysical properties of calcium channels. W e have used an HEK 293-based heterologous system which stably expresse s human neuronal calcium channels to address the relative contribution s of receptor, G protein, and channel to voltage-dependent inhibition. We find that the receptor and channel subtype only insignificantly in fluence the time it takes to re-establish modulation following voltage -dependent relief of inhibition. In contrast, the G protein subtype me diating inhibition appears to play a significant part in this process. These results emphasize the importance of G protein subtype in the mo dulation of neuronal calcium channels. (C) 1997 Elsevier Science Irela nd Ltd.