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Activation of nucleotide receptors inhibits M-type K current [I K(M)] in neuroblastoma × glioma hybrid cells

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  • Molecular and Cellular Physiology
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Abstract

A phospholipase-C-linked nucleotide receptor, sensitive to both uridine and adenosine triphosphate (UTP and ATP) has been cloned from NG108-15 neuroblastoma × glioma hybrid cells. We have tested whether activation of this receptor could inhibit the voltage-dependent K+ current [I K(M) or “M-current”] in NG108-15 cells recorded using whole-cell patch-clamp methods. Both UTP and ATP inhibited I K(M) by 44% and 42%, respectively, at 100 μM. Mean IC50 values were: UTP, 0.77±0.27 μM; ATP, 1.81±0.82 μM. The order of nucleotide and nucleoside activity at 100 μM was: UTP = ATP > ATP[γS] = ITP > 2 MeSATP > ADP = GTP ≫ AMP-CPP, adenosine, where ATP[γS] is adenosine 5′-O-(3-thiotriphosphate), ITP is inosine 5′-triphosphate, 2-MeSATP is 2-methylthio ATP and AMP-CPP is α,β methylene ATP. This rank order accords with their activities at the cloned P2U receptor. Effects were not inhibited by suramin (up to 500 μM) or by pre-incubation for 12 h in 500 ng·ml−1 Pertussis toxin. Inhibition of IK(M) was frequently preceded by a transient outward current, probably a Ca2+-activated K+ current, responding to Ca2+ mobilization. No effect on the delayed rectifier K+ current was observed. These observations match those expected from stimulating other phospholipase-C-linked receptors in NG108-15 cells.

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Authors and Affiliations

  1. Department of Pharmacology, University College London, Gower Street, WC1E 6BT, London, UK

    A. K. Filippov, A. A. Selyanko & D. A. Brown

  2. Pharmacology Group, Biomedical Sciences Division, King's College London, Manresa Road, SW3 6LX, London, UK

    J. Robbins

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  1. A. K. Filippov
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  2. A. A. Selyanko
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  3. J. Robbins
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  4. D. A. Brown
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Shemyakin Institute of Bio-organic Chemistry, on leave from the Russian Academy of Sciences, 142292 Pushchino, Moscow Region, Russia

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Filippov, A.K., Selyanko, A.A., Robbins, J. et al. Activation of nucleotide receptors inhibits M-type K current [I K(M)] in neuroblastoma × glioma hybrid cells. Pflugers Arch. 429, 223–230 (1994). https://doi.org/10.1007/BF00374316

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  • DOI: https://doi.org/10.1007/BF00374316

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