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- Title
T-type calcium channel regulation by specific G-protein b? subunits.
- Authors
Wolfe, Joshua T.; Wang, Hongge; Howard, Jason; Garrison, James C.; Barrett, Paula Q.
- Abstract
Low-voltage-activated (LVA) T-type calcium channels have a wide tissue distribution and have well-documented roles in the control of action potential burst generation and hormone secretion[SUP1]. In neurons of the central nervous system and secretory cells of the adrenal and pituitary, LVA channels are inhibited by activation of G-protein-coupled receptors that generate membrane-delimited signals[SUP2-5], yet these signals have not been identified. Here we show that the inhibition of α[SUB1H] (Ca[SUBv]3.2), but not α[SUB1G] (Ca[SUBv]3.1) LVA Ca[SUP2+] channels is mediated selectively by β[SUB2]γ[SUB2] subunits that bind)to the intracellular loop connecting channel transmembrane domains II and III. This region of the α[SUB1H] channel is crucial for inhibition, because its replacement abrogates inhibition and its transfer to non-modulated α[SUB1G] channels confers β[SUB2]γ[SUB2]-dependent inhibition. βγ reduces channel activity independent of voltage, a mechanism distinct from the established βγ-dependent inhibition of non-L-type high-voltage-activated channels of the Ca[SUBv]2 family[SUP6,7]. These studies identify the α[SUB1H] channel as a new effector for G-protein βγ subunits, and highlight the selective signalling roles available for particular βγ combinations.
- Subjects
CALCIUM channels; HORMONES; PROTEINS; NEURONS; NERVOUS system
- Publication
Nature, 2003, Vol 424, Issue 6945, p209
- ISSN
0028-0836
- Publication type
Article
- DOI
10.1038/nature01772