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Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation

Nature volume 361, pages 263–266 (1993)Cite this article

Abstract

NATRIURETIC peptides inhibit the release and action of many hormones through cyclic guanosine monophosphate (cGMP)1,2, but the mechanism of cGMP action is unclear3. In frog ventricular muscle and guinea-pig hippocampal neurons, cGMP inhibits voltage-activated Ca2+ currents by stimulating phosphodiesterase activity and reducing intracellular cyclic AMP4,5; however, this mechanism is not involved in the action of cGMP on other channels6 or on Ca2+ channels in other cells7,8. Natriuretic peptide receptors in the rat pituitary also stimulate guanylyl cyclase activity but inhibit secretion by increasing membrane conductance to potassium9,10. In an electrophysiological study on rat pituitary tumour cells11, we identified the large-conductance, calcium- and voltage-activated potassium channels (BK) as the primary target of another inhibitory neuropeptide, somatostatin. Here we report that atrial natriuretic peptide also stimulates BK channel activity in GH4C1 cells through protein dephosphorylation. Unlike somatostatin, however, the effect of atrial natriuretic peptide on BK channel activity is preceded by a rapid and potent stimulation of cGMP production and requires cGMP-dependent protein kinase activity. Protein phosphatase activation by cGMP-dependent kinase could explain the inhibitory effects of natriuretic peptides on electrical excitability and the antagonism of cGMP and cAMP in many systems12.

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Authors and Affiliations

  1. Laboratory of Cellular and Molecular Pharmacology, National Institute of Environmental Health Sciences, Research Triangle Park, North Carolina, 27709, USA

    R. E. White, A. D. Shcherbatko & D. L. Armstrong

  2. Department of Pharmacology, University of Texas Medical School, Houston, Texas, 77225, USA

    A. B. Lee & A. Schonbrunn

  3. Department of Pathology, University of Alabama, Birmingham, Alabama, 35294, USA

    T. M. Lincoln

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  1. R. E. White
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  5. A. Schonbrunn
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  6. D. L. Armstrong
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White, R., Lee, A., Shcherbatko, A. et al. Potassium channel stimulation by natriuretic peptides through cGMP-dependent dephosphorylation. Nature 361, 263–266 (1993). https://doi.org/10.1038/361263a0

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