G protein modulation of voltage-gated calcium channels.
Calcium influx into any cell requires fine tuning to guarantee the correct balance between activation of calcium-dependent processes, such as muscle contraction and neurotransmitter release, and calcium-induced cell damage. G protein-coupled receptors play a critical role in negative feedback to modulate the activity of the CaV2 subfamily of the voltage-dependent calcium channels, which are largely situated on neuronal and neuro-endocrine cells. The basis for the specificity of the relationships among membrane receptors, G proteins, and effector calcium channels will be discussed, as well as the mechanism by which G protein-mediated inhibition is thought to occur. The inhibition requires free G beta gamma dimers, and the cytoplasmic linker between domains I and II of the CaV2 alpha 1 subunits binds G beta gamma dimers, whereas the intracellular N terminus of CaV2 alpha 1 subunits provides essential determinants for G protein modulation. Evidence suggests a key role for the beta subunits of calcium channels in the process of G protein modulation, and the role of a class of proteins termed "regulators of G protein signaling" will also be described.
Dolphin
Annette C
AC
Department of Pharmacology, University College London, Gower St., London WC1E 6BT, UK. a.dolphin@ucl.ac.uk
D000818:Animals; D015220:Calcium Channels / Q000187:drug effects / Q000378:metabolism / Q000502:physiology*; D019204:GTP-Binding Proteins / Q000494:pharmacology / Q000502:physiology*; D006801:Humans; D008967:Molecular Biology
D015220:Calcium Channels; D019204:GTP-Binding Proteins