PMID- 8637575
OWN - NLM
STAT- MEDLINE
DCOM- 19960705
LR  - 20220309
IS  - 0028-0836 (Print)
IS  - 0028-0836 (Linking)
VI  - 380
IP  - 6571
DP  - 1996 Mar 21
TI  - Voltage-dependent modulation of N-type calcium channels by G-protein beta gamma 
      subunits.
PG  - 255-8
AB  - The most commonly used signal transduction pathway for receptor-mediated N-type 
      Ca2+-channel modulation involves activation of a heterotrimeric G protein to 
      produce voltage-dependent inhibition. Although it is widely assumed that Galpha 
      mediates this effect, experiments to address this hypothesis directly are 
      lacking. Here I show that transient overexpression of Gbetagamma in sympathetic 
      neurons mimics and occludes the voltage-dependent Ca2+ channel modulation 
      produced by noradrenaline (NA). Conversely, over-expression of Galpha produces 
      minimal effects on basal Ca2+ channel behaviour but attenuates NA-mediated 
      inhibition in a manner consistent with the buffering of Gbetagamma. These 
      observations indicate that it is Gbetagamma, and Galpha, that mediates 
      voltage-dependent inhibition of N-type Ca2+ channels. The identification of 
      Gbetagamma as the mediator of this pathway has broad implications as 
      G-protein-coupled receptors, many of which are implicated in disease or are 
      targets of therapeutic agents, couple to N-type Ca2+ channels and may modulate 
      synaptic transmission by this mechanism.
FAU - Ikeda, S R
AU  - Ikeda SR
AD  - Department of Pharmacology and Toxicology, Medical College of Georgia, Augusta 
      30912-2300, USA.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Nature
JT  - Nature
JID - 0410462
RN  - 0 (Calcium Channels)
RN  - 0 (DNA, Complementary)
RN  - 34273-04-6 (Guanylyl Imidodiphosphate)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - X4W3ENH1CV (Norepinephrine)
SB  - IM
MH  - Animals
MH  - Calcium Channels/chemistry/drug effects/*metabolism
MH  - Cattle
MH  - Culture Techniques
MH  - DNA, Complementary
MH  - Electrochemistry
MH  - GTP-Binding Proteins/genetics/*metabolism
MH  - Guanylyl Imidodiphosphate/pharmacology
MH  - Neurons/*metabolism
MH  - Norepinephrine/pharmacology
MH  - Rats
MH  - Sympathetic Nervous System/cytology/metabolism
EDAT- 1996/03/21 00:00
MHDA- 1996/03/21 00:01
CRDT- 1996/03/21 00:00
PHST- 1996/03/21 00:00 [pubmed]
PHST- 1996/03/21 00:01 [medline]
PHST- 1996/03/21 00:00 [entrez]
AID - 10.1038/380255a0 [doi]
PST - ppublish
SO  - Nature. 1996 Mar 21;380(6571):255-8. doi: 10.1038/380255a0.