PT  - JOURNAL ARTICLE
AU  - Annette C. Dolphin
TI  - G Protein Modulation of Voltage-Gated Calcium Channels
AID  - 10.1124/pr.55.4.3
DP  - 2003 Dec 01
TA  - Pharmacological Reviews
PG  - 607--627
VI  - 55
IP  - 4
4099  - http://pharmrev.aspetjournals.org/content/55/4/607.short
4100  - http://pharmrev.aspetjournals.org/content/55/4/607.full
SO  - Pharmacol Rev2003 Dec 01; 55
AB  - 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 Gβγ dimers, and the cytoplasmic linker between domains I and II of the CaV2 α1 subunits binds Gβγ dimers, whereas the intracellular N terminus of CaV2 α1 subunits provides essential determinants for G protein modulation. Evidence suggests a key role for the β 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.