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

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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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Author notes

  1. David E. Clapham: To whom correspondence should be addressed

Authors and Affiliations

  1. Department of Pharmacology, Mayo Foundation, Rochester, Minnesota, 55905, USA

    Kevin D. Wickman, Philip A. Davenport, Grigory B. Krapivinsky & David E. Clapham

  2. Department of Pharmacology, University of Texas Southwestern Medical Center, Dallas, Texas, 75235, USA

    Jorge A. Iñiguez-Lluhi, Ronald Taussig, Maurine E. Linder & Alfred G. Gilman

Authors
  1. Kevin D. Wickman
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  2. Jorge A. Iñiguez-Lluhi
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  3. Philip A. Davenport
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  4. Ronald Taussig
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  5. Grigory B. Krapivinsky
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  6. Maurine E. Linder
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  7. Alfred G. Gilman
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  8. David E. Clapham
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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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