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. 1990;30(Suppl 1):13S–22S. doi: 10.1111/j.1365-2125.1990.tb05463.x

G protein coupling of receptors to ionic channels and other effector systems

L Birnbaumer, A Yatani, A M J Vandongen, R Graf, J Codina, K Okabe, R Mattera, A M Brown
PMCID: PMC1368093  PMID: 1702677

Abstract

1 Four questions raised by previous studies that had shown activation of K+ channels by α subunits of the type 3 Gi protein are addressed in the present communication: a) are K+ channels specific for one Gi? b) are there more ionic channels under direct G protein control? c) can we confirm using recombinant Gαs the results obtained with biochemically resolved Gαs and continue ascribing the regulatory effector to this part of the αβγ holo-G protein? and d) can we confirm that a single Gα, Gsα in this case, is able to affect more than one type of effector function?

2 We found Giαs are isoforms, that there exist also Gi-insensitive, Go-responsive K+ channels and that Gαs can be multifunctional. Thus, a single receptor will elicit cellular responses that will depend on the endogenous G protein as well as the type of effector function expressed in it.

3 In another set of experiments we found that Gβγs, be they derived from human erythrocytes, human placenta, bovine brain or bovine retina, all inhibit Gk-gated K+ channel activity as seen in inside out membrane patches with GTP as the driving nucleotide. In addition we noted that inhibition was much more effective under basal (no agonist in the pipette) than agonist stimulated conditions, as reported in earlier experiments in which β-adrenoceptors, Gs and catalytic unit of adenylyl cyclase had been incorporated into phospholipid vesicles.

4 We propose that one of the roles of Gβγs in membranes is to quench ligand independent G protein activation by unoccupied receptors. Other roles of Gβγs are: a) by re-associating with GDP-Gαs, to promote interaction with receptors, and b) by dissociating from activated R.Gα*GTP·βγ, to allow for receptor dissociation from GTP-activated Gαs, which is required to satisfy the catalytic mode of receptor action.

Keywords: G protein, K+ channels

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Selected References

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