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Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells

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Abstract

Caffeine elicits physiological responses in a variety of cell types by triggering the mobilization of Ca2+ from intracellular organelles. Here we investigate the effects of caffeine on intracellular Ca2+ concentration ([Ca2+]i) and ionic currents in anterior pituitary cells (GH3) cells. Caffeine has a biphasic effect on Ca2+-activated K+ current [I K(Ca)]: it induces a transient increase superimposed upon a sustained inhibition. While the transient increase coincides with a rise in [Ca2+]i, the sustained inhibition of I K(Ca) is correlated with a sustained inhibition of the L-type Ca2+ current. The L-type Ca2+ current is also inhibited by other agents that mobilize intracellular Ca2+, including thyrotropin releasing hormone (TRH) and ryanodine, but in a matter distinct from caffeine. Unlike the caffeine effect, the TRH-induced inhibition “washes-out” under whole-cell patch-clamp conditions and is eliminated by intracellular Ca2+ chelators. Likewise, the ryanodine-induced inhibition desensitizes while the caffeine-induced inhibition does not. Simultaneous [Ca2+]i and Ca2+ current measurements show that caffeine can inhibit Ca2+ current without changing [Ca2+]i. Single-channel recordings show that caffeine reduces mean open time without affecting single-channel conductance of L-type channels. Hence the effects of caffeine on ion channels in GH3 cells are attributable both to mobilization of intracellular Ca2+ and to a direct effect on the gating of L-type Ca2+ channels.

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Author notes

  1. Richard H. Kramer

    Present address: Department of Molecular and Cellular Pharmacology, University of Miami School of Medicine, P. O. Box 016189, 33101, Miami, FL, USA

Authors and Affiliations

  1. Center for Neurobiology and Behavior, Columbia University of Physicians and Surgeons, 722 West 168th Street, 10032, New York, NY, USA

    Richard H. Kramer

  2. Department of Pharmacology, University of Pittsburgh School of Medicine, 15261, Pittsburgh, PA, USA

    Rupa Mokkapatti & Edwin S. Levitan

Authors
  1. Richard H. Kramer
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  2. Rupa Mokkapatti
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  3. Edwin S. Levitan
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Kramer, R.H., Mokkapatti, R. & Levitan, E.S. Effects of caffeine on intracellular calcium, calcium current and calcium-dependent potassium current in anterior pituitary GH3 cells. Pflugers Arch. 426, 12–20 (1994). https://doi.org/10.1007/BF00374665

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  • DOI: https://doi.org/10.1007/BF00374665

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