Abstract
Cholinergic muscarinic, serotonergic, opioid and several other G-protein-coupled neurotransmitter receptors activate inwardly rectifying K+ channels of the GIRK family, slowing the heartbeat and decreasing the excitability of neuronal cells. Inhibitory modulation of GIRKs by G-protein-coupled receptors may have important implications in cardiac and brain physiology. Previously G(α) and G(βγ) Subunits of heterotrimeric G proteins have both been implicated in channel opening, but recent studies attribute this role primarily to the G(βγ) dimer that activates GIRKs in a membrane-delimited fashion, probably by direct binding to the channel protein. We report here that free GTPγS-activated G(αi1), but not G(αi2) or G(αi3), potently inhibits G(β1γ2)-induced GIRK activity in excised membrane patches of Xenopus oocytes expressing GIRK1. High-affinity but partial inhibition is produced by G(αs)-GTPγS. G(αi1)-GTPγS also inhibits G(β1γ2)-activated GIRK in atrial myocytes. Antagonistic interactions between G(α) and G(βγ) may be among the mechanisms determining specificity of G protein coupling to GIRKs.
Original language | English (US) |
---|---|
Pages (from-to) | 624-627 |
Number of pages | 4 |
Journal | Nature |
Volume | 380 |
Issue number | 6575 |
DOIs | |
State | Published - Apr 18 1996 |
ASJC Scopus subject areas
- General