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The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator

Nature volume 360, pages 81–84 (1992)Cite this article

Abstract

STIMULATION of β-adrenoceptors in cardiac ventricular myocytes activates a strong chloride ion conductance1–5 as a result of phosphorylation by cyclic AMP-dependent protein kinase (PKA)2,4. This Cl− conductance, which is time- and voltage-independent1,5, counters2,5 the tendency of the simultaneously enhanced Ca2+ channel current to prolong the ventricular action potential. Using inside-out giant patches6 excised from guinea-pig myocytes, we show here that phosphorylation by the PKA catalytic subunit plus Mg-ATP elicits discrete Cl− channel currents. In almost symmetrical Cl− solutions (∼150 mM), unitary current amplitude scales with membrane potential, and reverses sign near 0 mV, to yield a single channel conductance of ∼12 pS. Opening of the phosphorylated channels requires hydrolysable nucleoside triphosphate, indicating that phosphorylation by PKA is necessary, but not sufficient, for channel activation. The properties of these PKA-regulated cardiac Cl− channels are very similar, if not identical, to those of the cystic fibrosis transmembrane conductance regulator (CFTR)7, the epithelial cell Cl− channel whose regulation is defective in patients with cystic fibrosis. The full cardiological impact of these Cl− channels and of their possible malfunction in patients with cystic fibrosis remains to be determined.

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Author notes

  1. Kent L. Nastiuk and Angus C. Nairn: Laboratory of Molecular and Cellular Neuroscience, The Rockefeller University, 1230 York Avenue, New York, New York 10021-6399, USA

Authors and Affiliations

  1. Laboratory of Cardiac/Membrane Physiology,

    Georg Nagel, Tzyh-Chang Hwang, Kent L. Nastiuk, Angus C. Nairn & David C. Gadsbyt

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  1. Georg Nagel
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  2. Tzyh-Chang Hwang
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  4. Angus C. Nairn
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  5. David C. Gadsbyt
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Nagel, G., Hwang, TC., Nastiuk, K. et al. The protein kinase A-regulated cardiac CI− channel resembles the cystic fibrosis transmembrane conductance regulator. Nature 360, 81–84 (1992). https://doi.org/10.1038/360081a0

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