Selective regulation of N-type Ca channels by different combinations of G-protein beta/gamma subunits and RGS proteins.
We examined the effects of G-protein beta and gamma subunit heterodimers on human alpha(1B) (N-type) Ca channels expressed in HEK293 cells. All of the known beta subunits (beta1-beta5) produced voltage-dependent inhibition of alpha(1B) Ca channels, depending on the gamma subunit found in the heterodimer. beta1-beta4 subunits inhibited Ca channels when paired with gamma1-gamma3. However, beta5 subunits only produced inhibition when paired with gamma2. In contrast, heterodimers between beta5 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 Gbeta5/gamma2 heterodimers to inhibit Ca channels. Because all of the G-protein beta 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 Gbeta5gamma2 suggests a novel way in which Ca channels can be regulated.
Zhou
J Y
JY
Department of Neurobiology, Pharmacology, and Physiology, University of Chicago, Chicago, Illinois 60637, USA.
Siderovski
D P
DP
Miller
R J
RJ
D000704:Analysis of Variance; D000818:Animals; D001464:Barium / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000378:metabolism*; D002478:Cells, Cultured; D003001:Cloning, Molecular; D003587:Cytomegalovirus / Q000235:genetics; D019281:Dimerization; D015870:Gene Expression; D020962:Heterotrimeric GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D007668:Kidney / Q000166:cytology / Q000378:metabolism; D008564:Membrane Potentials / Q000187:drug effects; D051379:Mice; D020710:RGS Proteins / Q000378:metabolism*; D012333:RNA, Messenger / Q000096:biosynthesis; D014162:Transfection
D020864:Calcium Channels, N-Type; D020710:RGS Proteins; D012333:RNA, Messenger; D001464:Barium; D020962:Heterotrimeric GTP-Binding Proteins