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The Journal of Neuroscience, October 1, 2000, 20(19):7143-7148

Selective Regulation of N-Type Ca Channels by Different Combinations of G-Protein / Subunits and RGS Proteins

Janice Y. Zhou¹, David P. Siderovski², and Richard J. Miller¹

¹ Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, and ² Department of Pharmacology, University of North Carolina, Chapel Hill, North Carolina 27599

We examined the effects of G-protein  and  subunit heterodimers on human _1B (N-type) Ca channels expressed in HEK293 cells. All of the known  subunits (1-5) produced voltage-dependent inhibition of _1B Ca channels, depending on the  subunit found in the heterodimer. 1-4 subunits inhibited Ca channels when paired with 1-3. However, 5 subunits only produced inhibition when paired with 2. In contrast, heterodimers between 5 subunits and RGS (regulators of G-protein signaling) proteins containing GGL domains did not produce inhibition of Ca channels. However, GGL domain-containing RGS proteins (e.g., RGS6 and RGS11) did block the ability of G5/2 heterodimers to inhibit Ca channels. Because all of the G-protein  subunits are found in the nervous system, we conclude that they may all potentially participate in Ca channel inhibition. The interaction of GGL-containing RGS proteins with G52 suggests a novel way in which Ca channels can be regulated.

Key words: heterotrimeric G-proteins; calcium channel; ion-channel modulation; RGS proteins; presynaptic inhibition; synaptic transmission

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Copyright © 2000 Society for Neuroscience  0270-6474/00/20197143-06$05.00/0

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