Muscarinic K+ channels are activated by beta gamma subunits and inhibited by the GDP-bound form of alpha subunit of transducin.

It was reported that transducin beta gamma subunits (T beta gamma) inhibited cardiac muscarinic K+ (KACh) channels activated through GK. This result has been used to support the proposal that GK activates this channel through its alpha subunits. Here, we have reexamined the effects of transducin subunits on KACh channels. T beta gamma applied to the internal side of the inside-out patch membrane activated KACh channels in a concentration-dependent manner (EC50 approximately 1 microM). In contrast, the GDP-bound form of transducin alpha subunits (50 nM-3 microM), but not T beta gamma (1 nM-1 microM), irreversibly inhibited KACh channel openings induced either by GTP plus acetylcholine or by GTP gamma S (guanosine 5'-3-O-(thio)triphosphate). This inhibition was antagonized by exogenously applied T beta gamma (600 nM-3 microM) or brain G protein beta gamma subunits (10-30 nM). These data, opposite to the previous report, indicate that GK activates KACh channels through its beta gamma subunits.