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Acetylcholine and adenosine activate the G protein-gated muscarinic K+ channel in ferret ventricular myocytes

Naunyn-Schmiedeberg's Archives of Pharmacology volume 351, pages 610–617 (1995)Cite this article

Abstract

The properties of the K+ channel activated by acetylcholine (ACh) and adenosine (Ado) were examined in single ferret ventricular myocytes using patch-clamp techniques. In the whole-cell configuration, ACh and Ado induced an inwardly rectifying K+ current and shortened the action potential duration. The effect of ACh was blocked by atropine, while the Ado effect was interrupted by 8-cyclopenty1,1,2-dipropyl xanthine, a specific Ado A1 receptor antagonist. In cell-attached recordings, ACh and Ado added to the pipette solution activated a single population of inwardly rectifying K+ channels, distinct from the i K1 channel. The channel had a slope conductance of ∼ 40 pS in symmetrical 150 mM K+ solutions and a mean open time of 0.8 ms. Excision of the patch into the inside-out patch configuration in guanosine triphosphate (GTP)-free solution abolished the channel activity. The channel was reversibly reactivated by adding GTP to the intracellular side of the patch. GTPγS activated the channel irreversibly. When the inside-out patch was treated with the A protomer of pertussis toxin (PTX), intracellular GTP no longer activated the K+ channel. The results show that ferret ventricular myocytes possess a K+ channel activated by both muscarinic and Ado A1 receptors. Its electrophysiological properties and the gating by a PTX-sensitive G protein in a membrane-delimited fashion are identical with those of the muscarinic K+ channels in nodal and atrial tissues of other species. In conclusion, the G protein-gated muscarinic K+ channel is expressed in ferret ventricular myocardium and may underlie the direct negative inotropism of ACh and Ado in this tissue.

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Affiliations

  1. Department of Cell Biology and Signaling, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-23, Yamagata, Japan

    H. Ito, Y. Hosoya & A. Inanobe

  2. The First Department of Internal Medicine, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-23, Yamagata, Japan

    H. Tomoike

  3. Department of Pharmacology, Yamagata University School of Medicine, Iida-nishi 2-2-2, 990-23, Yamagata, Japan

    M. Endoh

Authors
  1. H. Ito
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  2. Y. Hosoya
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  3. A. Inanobe
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  4. H. Tomoike
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  5. M. Endoh
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Ito, H., Hosoya, Y., Inanobe, A. et al. Acetylcholine and adenosine activate the G protein-gated muscarinic K+ channel in ferret ventricular myocytes. Naunyn-Schmiedeberg's Arch Pharmacol 351, 610–617 (1995). https://doi.org/10.1007/BF00170160

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  • DOI: https://doi.org/10.1007/BF00170160

Key words

  • Ferret
  • Ventricular myocytes
  • Acetylcholine
  • Adenosine
  • Muscarinic K+
  • channel
  • G protein