Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel

Abstract

ACETYLCHOLINE activates inwardly rectifying potassium channels (Ik.ACh) in the heart1 through muscarinic receptor binding and activation of pertussis-toxin-sensitive G proteins2,3. Experiments showing that only the βγ-subunit (Gβγ) activates IK.ACH (ref. 4) were challenged by reports that only the activated α-subunit (Gα) was effective5. Here we examine IK.ACh regulation using purified brain and recombinant G-protein subunits. Six recombinant Gβγ-subunits activated IK.ACh with apparent half-maximal activation concentrations of 3-30 nM. Activation of IK.ACh by recombinant Gα-GTPγS was observed, but this was probably due to release of GTPγS from the protein. Importantly, IK.ACh activity elicited by GTPγS was inhibited by purified brain and recombinant Gα-GDP, suggesting that native Gβγ plays a major role in this pathway. We conclude that Gβγ is a primary regulator of IK.ACh activity.

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Wickman, K., Iñiguez-Lluhi, J., Davenport, P. et al. Recombinant G-protein βγ-subunits activate the muscarinic-gated atrial potassium channel. Nature 368, 255–257 (1994). https://doi.org/10.1038/368255a0

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