TY - JOUR
T1 - Gαi controls the gating of the G protein-activated K+ channel, GIRK
AU - Peleg, Sagit
AU - Varon, Dalia
AU - Ivanina, Tatiana
AU - Dessauer, Carmen W.
AU - Dascal, Nathan
N1 - Funding Information:
We are grateful to the colleagues who kindly provided the original cDNA clones: E. Peralta (m2R), P. Kofuji and H. Lester (GIRK2), M. Simon (G protein subunits), E. Reuveny (cβARK), E. Liman (pGEMHE), and L. Salkoff (pBS-MXT). We thank R. Barzilai for expert technical assistance, A. Mittelman and A. Barbul for help with confocal microscopy, E. Reuveny for helpful suggestions, D. Singer-Lahat for advice in immunohistochemical and biochemical experiments, I. Lotan for the critical reading of the manuscript, and an anonymous reviewer for helpful and constructive critique. This work was supported by the NIH (GM 56260-01).
PY - 2002/1/3
Y1 - 2002/1/3
N2 - GIRK (Kir3) channels are activated by neurotransmitters coupled to G proteins, via a direct binding of Gβγ. The role of Gα subunits in GIRK gating is elusive. Here we demonstrate that Gαi is not only a donor of Gβγ but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or Gβγ. Coexpression of Gαi3 or Gαi1 restores the correct gating parameters. Gαi acts neither as a pure Gβγ scavenger nor as an allosteric cofactor for Gβγ. It inhibits only the basal activity without interfering with Gβγ-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. Gαi probably acts in its GDP bound form, alone or as a part of Gαβγ heterotrimer.
AB - GIRK (Kir3) channels are activated by neurotransmitters coupled to G proteins, via a direct binding of Gβγ. The role of Gα subunits in GIRK gating is elusive. Here we demonstrate that Gαi is not only a donor of Gβγ but also regulates GIRK gating. When overexpressed in Xenopus oocytes, GIRK channels show excessive basal activity and poor activation by agonist or Gβγ. Coexpression of Gαi3 or Gαi1 restores the correct gating parameters. Gαi acts neither as a pure Gβγ scavenger nor as an allosteric cofactor for Gβγ. It inhibits only the basal activity without interfering with Gβγ-induced response. Thus, GIRK is regulated, in distinct ways, by both arms of the G protein. Gαi probably acts in its GDP bound form, alone or as a part of Gαβγ heterotrimer.
UR - http://www.scopus.com/inward/record.url?scp=0037012061&partnerID=8YFLogxK
U2 - 10.1016/S0896-6273(01)00567-0
DO - 10.1016/S0896-6273(01)00567-0
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AN - SCOPUS:0037012061
SN - 0896-6273
VL - 33
SP - 87
EP - 99
JO - Neuron
JF - Neuron
IS - 1
ER -