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Regulation of Ca2+ -dependent K+ -channel activity in tracheal myocytes by phosphorylation

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Abstract

ISOPRENALINE is a (β-adrenergic agonist of clinical importance as a remedy for asthma. In airway smooth muscle its relaxant action is accompanied by hyperpolarization of the membrane1,2 and elevation of the level of intracellular cyclic AMP3. Hyper-polarization and relaxation are also induced by drugs such as forskolin, theophylline and dibutyryl cAMP, indicating that cAMP-dependent phosphorylation is involved in producing the electrical response1. Cyclic AMP-dependent protein kinase (pro-tein kinase A) has been reported to activate Ca2+-dependent K+ channels in cultured aortic smooth muscle cells4 and snail neurons5,6. The membrane of tracheal smooth-muscle cells is characterized by a dense distribution of Ca2+-dependent K+-channels7. We have now examined the effect of isoprenaline and protein kinase A on Ca2+-dependent K+-channels in isolated smooth muscle cells of rabbit trachea, using the patch-clamp technique8. Our results show that the open-state probability of Ca2+-dependent K+-channel of tracheal myocytes is reversibly increased by either extracellular application of isoprenaline or intracellar application of protein kinase A. We also show that this effect is significantly enhanced and prolonged in the presence of a potent protein phos-phatase inhibitor, okadaic acid9–13.

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Authors and Affiliations

  1. The Second Department of Internal Medicine, School of Medicine, Nagoya University, Tsurumai-cho 65, Showa-ku, Nagoya, 466, Japan

    H. Kume

  2. Department of Physiology, School of Medicine, Nagoya University, Tsurumai-cho 65, Showa-ku, Nagoya, 466, Japan

    A. Takai, H. Tokuno & T. Tomita

Authors
  1. H. Kume
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  2. A. Takai
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  3. H. Tokuno
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  4. T. Tomita
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Kume, H., Takai, A., Tokuno, H. et al. Regulation of Ca2+ -dependent K+ -channel activity in tracheal myocytes by phosphorylation. Nature 341, 152–154 (1989). https://doi.org/10.1038/341152a0

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