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Dual regulation of M current in gastric smooth muscle cells: β-adrenergic-muscarinic antagonism

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Abstract

The effects of the β-adrenergic agent isoproterenol on membrane currents were studied in freshly dissociated gastric smooth muscle cells of Bufo marinus. Voltage-clamp experiments were carried out with patch pipettes in the tight-seal, whole-cell recording mode or with conventional microelectrodes. Isoproterenol induced a current identified as M current by the following criteria: the induced current is outward and carried by K+ ions, is suppressed by muscarine or acetylcholine, remains steadily activated, turns off with hyperpolarization, and exhibits slow relaxations in response to voltage jumps. In contrast to endogenous M current, isoproterenol-induced M current usually exhibited slower relaxations on hyperpolarizing voltage commands and displayed a steady-state conductance/voltage relationship that was shifted in the negative direction along the voltage axis. M current was also induced by either forskolin or phosphodiesterase-resistant cAMP analogs. In all cases, muscarinic agonists suppressed the M current, apparently by acting at a locus downstream from regulation of cAMP levels by adenylate cyclase and phosphodiesterase. β-Adrenergic agents may act to increase the number of M channels available to be opened and also modify their kinetics.

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Author notes

  1. Stephen M. Sims

    Present address: Department of Physiology, The University of Western Ontario, N6A 5C1, London, Ontario, Canada

  2. Lucie H. Clapp

    Present address: Department of Pharmacology, UMDS, St. Thomas's Campus, Lambeth Palace Road, SE1 7EH, London, UK

Authors and Affiliations

  1. Department of Physiology, University of Massachusetts Medical School, 01655, Worcester, MA, USA

    Stephen M. Sims, Lucie H. Clapp, John V. Walsh Jr & Joshua J. Singer

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  1. Stephen M. Sims
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  3. John V. Walsh Jr
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  4. Joshua J. Singer
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Sims, S.M., Clapp, L.H., Walsh, J.V. et al. Dual regulation of M current in gastric smooth muscle cells: β-adrenergic-muscarinic antagonism. Pflugers Arch. 417, 291–302 (1990). https://doi.org/10.1007/BF00370995

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  • DOI: https://doi.org/10.1007/BF00370995

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