Biophys J, August 2000, p. 731-746, Vol. 79, No. 2

Calcium Channel  Subunit Promotes Voltage-Dependent Modulation of 1B by G

Department of Pharmacology, University College London, London WC1E 6BT, United Kingdom

Voltage-dependent calcium channels (VDCCs) are heteromultimers composed of a pore-forming 1 subunit and auxiliary subunits, including the intracellular  subunit, which has a strong influence on the channel properties. Voltage-dependent inhibitory modulation of neuronal VDCCs occurs primarily by activation of G-proteins and elevation of the free G dimer concentration. Here we have examined the interaction between the regulation of N-type (1B) channels by their  subunits and by G dimers, heterologously expressed in COS-7 cells. In contrast to previous studies suggesting antagonism of G protein inhibition by the VDCC  subunit, we found a significantly larger G-dependent inhibition of 1B channel activation when the VDCC 1B and  subunits were coexpressed. In the absence of coexpressed VDCC  subunit, the G dimers, either expressed tonically or elevated via receptor activation, did not produce the expected features of voltage-dependent G protein modulation of N-type channels, including slowed activation and prepulse facilitation, while VDCC  subunit coexpression restored all of the hallmarks of G modulation. These results suggest that the VDCC  subunit must be present for G to induce voltage-dependent modulation of N-type calcium channels.

Biophys J, August 2000, p. 731-746, Vol. 79, No. 2
© 2000 by the Biophysical Society   0006-3495/00/08/731/16  $2.00

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