G protein modulation of voltage-gated calcium channels

被引:213
作者
Dolphin, AC [1 ]
机构
[1] UCL, Dept Pharmacol, London WC1E 6BT, England
关键词
D O I
10.1124/pr.55.4.3
中图分类号
R9 [药学];
学科分类号
1007 ;
摘要
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 Ca(V)2 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 Gbetagamma dimers, and the cytoplasmic linker between domains I and II of the Ca(V)2 alpha1 subunits binds Gbetagamma dimers, whereas the intracellular N terminus of Ca(V)2 alpha1 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.
引用
收藏
页码:607 / 627
页数:21
相关论文
共 193 条
[1]   DIALYSIS OF LACTOTROPES WITH ANTISENSE OLIGONUCLEOTIDES ASSIGNS GUANINE-NUCLEOTIDE BINDING-PROTEIN SUBTYPES TO THEIR CHANNEL EFFECTORS [J].
BAERTSCHI, AJ ;
AUDIGIER, Y ;
LLEDO, PM ;
ISRAEL, JM ;
BOCKAERT, J ;
VINCENT, JD .
MOLECULAR ENDOCRINOLOGY, 1992, 6 (12) :2257-2265
[2]   Ducky mouse phenotype of epilepsy and ataxia is associated with mutations in the Cacna2d2 gene and decreased calcium channel current in cerebellar Purkinje cells [J].
Barclay, J ;
Balaguero, N ;
Mione, M ;
Ackerman, SL ;
Letts, VA ;
Brodbeck, J ;
Canti, C ;
Meir, A ;
Page, KM ;
Kusumi, K ;
Perez-Reyes, E ;
Lander, ES ;
Frankel, WN ;
Gardiner, RM ;
Dolphin, AC ;
Rees, M .
JOURNAL OF NEUROSCIENCE, 2001, 21 (16) :6095-6104
[4]   Biophysical properties, pharmacology, and modulation of human, neuronal L-type (α1D, Cav1.3) voltage-dependent calcium currents [J].
Bell, DC ;
Butcher, AJ ;
Berrow, NS ;
Page, KM ;
Brust, PF ;
Nesterova, A ;
Stauderman, KA ;
Seabrook, GR ;
Nürnberg, B ;
Dolphin, AC .
JOURNAL OF NEUROPHYSIOLOGY, 2001, 85 (02) :816-827
[5]   Properties of cloned rat alpha 1A calcium channels transiently expressed in the COS-7 cell line [J].
Berrow, NS ;
Brice, NL ;
Tedder, I ;
Page, KM ;
Dolphin, AC .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1997, 9 (04) :739-748
[6]   ANTISENSE DEPLETION OF BETA-SUBUNITS MODULATES THE BIOPHYSICAL AND PHARMACOLOGICAL PROPERTIES OF NEURONAL CALCIUM CHANNELS [J].
BERROW, NS ;
CAMPBELL, V ;
FITZGERALD, EM ;
BRICKLEY, K ;
DOLPHIN, AC .
JOURNAL OF PHYSIOLOGY-LONDON, 1995, 482 (03) :481-491
[7]   Mechanism of action of Gq to inhibit Gβγ modulation of Cav2.2 calcium channels:: Probed by the use of receptor-Gα tandems [J].
Bertaso, F ;
Ward, RJ ;
Viard, P ;
Milligan, G ;
Dolphin, AC .
MOLECULAR PHARMACOLOGY, 2003, 63 (04) :832-843
[8]   The I-II loop of the Ca2+ channel α1 subunit contains an endoplasmic reticulum retention signal antagonized by the β subunit [J].
Bichet, D ;
Cornet, V ;
Geib, S ;
Carlier, E ;
Volsen, S ;
Hoshi, T ;
Mori, Y ;
De Waard, M .
NEURON, 2000, 25 (01) :177-190
[9]   Structures and functions of calcium channel β subunits [J].
Birnbaumer, L ;
Qin, N ;
Olcese, R ;
Tareilus, E ;
Platano, D ;
Costantin, J ;
Stefani, E .
JOURNAL OF BIOENERGETICS AND BIOMEMBRANES, 1998, 30 (04) :357-375
[10]   Identification and cloning of putative human neuronal voltage-gated calcium channel γ-2 and γ-3 subunits:: Neurologic implications [J].
Black, JL ;
Lennon, VA .
MAYO CLINIC PROCEEDINGS, 1999, 74 (04) :357-361