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Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes

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Summary

Effects of verapamil on the acetylcholine (ACh)-induced K+ current were examined in single atrial cells, using the tight-seal whole-cell clamp technique. The pipette solution contained guanosine-5′-triphosphate (GTP) or guanosine-5′-O-(3-thiotriphosphate) (GTP-γS, a non-hydrolysable GTP analogue). In GTP-loaded cells, ACh induced a specific K+ current, which is known to be mediated by pertussis toxin-sensitive GTP-binding (G) proteins. Verapamil (0.1–100 μM) depressed the ACh-induced K+ current in a concentration-dependent fashion. In GTP-γS-loaded cells, the K+ current remained persistently after wash-out of ACh, probably due to irreversible activation of G proteins by GTP-γS. Verapamil (0.1–100 μM) also depressed the intracellular GTP-γS-induced K+ current. However, the magnitude of verapamil-depression of the K+ current in GTP-γS-loaded cells was significantly smaller than that in GTP-loaded cells at concentrations between 1 and 10 μM of the drug. From these results, it is suggested that verapamil may block not only the function of muscarinic ACh receptors but also of G proteins and/or the K+ channel itself and thereby depress the ACh-induced K+ current in isolated atrial myocytes.

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Supported by grants from the Ministry of Education, Science and Culture of Japan and the Research Program on Ca Signal Control

Send offprint requests to Y. Kurachi at the above address

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Ito, H., Takikawa, R., Kurachi, Y. et al. Anti-cholinergic effect of verapamil on the muscarinic acetylcholine receptor-gated K+ channel in isolated guinea-pig atrial myocytes. Naunyn-Schmiedeberg's Arch Pharmacol 339, 244–246 (1989). https://doi.org/10.1007/BF00165150

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  • DOI: https://doi.org/10.1007/BF00165150

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