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A Calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells

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Abstract

We recently reported that M-1 mouse cortical collecting duct cells show nonselective cation (NSC) channel activity (Proc. Natl. Acad. Sci. USA 89:10262–10266, 1992). In this study, we further characterize the M-1 NSC channel using single-channel current recordings in excised inside-out patches. The M-1 NSC channel does not discriminate between Na+, K+, Rb+, Cs+, and Li+. It has a linear I-V relation with a conductance of 22.7±0.5 pS (n=78) at room temperature. The Pcation/ Panion ratio is about 60 and there is no measurable conductance for NMDG, Ca2+, Ba2+, and Mn2+. Cytoplasmic calcium activates the M-1 NSC channel at a threshold of 10−6 m and depolarization increases channel activity (NP o ). Cytoplasmic application of adenine nucleotides inhibits the M-1 NSC channel. At doses of 10−4 m and 10−3 m, ATP reduces NP o by 23% and 69%, respectively.

Furthermore, since ADP (10−3 m) reduces NP o by 93%, the inhibitory effect of adenine nucleotides is not dependent on the presence of a γ-phosphoryl group and therefore does not involve protein phosphorylation. The channel is not significantly affected by 8-Br-cGMP (10−4 m) or by cGMP-dependent protein kinase (10−7 m) in the presence of 8-Br-cGMP (10−5 m) and ATP (10−4 m). The NSC channel is not sensitive to amiloride (10−4 m cytoplasmic and/or extracellular) but flufenamic acid (10−4 m) produces a voltage-dependent block, reducing NP o by 35% at depolarizing voltages and by 80% at hyperpolarizing voltages.

We conclude that the NSC channel of M-1 mouse cortical collecting duct cells belongs to an emerging family of calcium-activated and nucleotide-sensitive nonselective cation channels. It does not contribute to amiloride-sensitive sodium absorption and is unlikely to be a major route for calcium entry. The channel is normally quiescent but may be activated under special physiological conditions, e.g., during volume regulation.

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Authors and Affiliations

  1. Zentrum der Physiologie, Klinikum der Johann Wolfgang Goethe Universität, Frankfurt am Main, Germany

    C. Korbmacher, T. Volk & E. Frömter

  2. Department of Cellular and Molecular Physiology, Yale University, School of Medicine, New Haven, CT

    C. Korbmacher, A. S. Segal & E. L. Boulpaep

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  1. C. Korbmacher
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  2. T. Volk
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  3. A. S. Segal
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  4. E. L. Boulpaep
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  5. E. Frömter
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The expert technical assistance of U. Fink and I. Doering-Hirsch is gratefully acknowledged. We thank A. Rabe and Dr. J. Disser for programming the computer software.

This work was supported by a grant from the Deutsche Forschungsge-meinschaft (DFG grant Fr 233/9-1) and a grant from the National Institutes of Health (NIH grant DK-17433).

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Korbmacher, C., Volk, T., Segal, A.S. et al. A Calcium-activated and nucleotide-sensitive nonselective cation channel in M-1 mouse cortical collecting duct cells. J. Membarin Biol. 146, 29–45 (1995). https://doi.org/10.1007/BF00232678

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