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Modulation of Ca2+ oscillation and apamin-sensitive, Ca2+-activated K+ current in rat gonadotropes

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  • Molecular and Cellular Physiology
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Abstract

In rat pituitary gonadotropes, gonadotropin-releasing hormone (GnRH) stimulates rhythmic release of Ca2+ from stores sensitive to inositol 1,4,5-trisphosphate [Ins(1,4,5)P 3 ], which in turn induces an oscillatory activation of apamin-sensitive Ca2+-activated K+ current, I K(Ca). Since GnRH also activates protein kinase C (PKC), we investigate the action of PKC while simultaneously measuring intracellular Ca2+ concentration ([Ca2+]i) and I K(Ca). Stimulation of PKC by application of phorbol 12-myristate 13-acetate (PMA) did not affect basal [Ca2+]i. However, PMA or phorbol 12,13-dibutyrate (PdBu), but not the inactive 4α-phorbol 12,13-didecanoate (4α-PDD), reduced the frequency of GnRH-induced [Ca2+]i oscillation and augmented the I K(Ca) induced by any given level of [Ca2+]i. The slowing of oscillations and the enhancement of I K(Ca) were mimicked by synthetic diacylglycerol (1,2-dioctanoyl-sn-glycerol) and could be induced during ongoing oscillations that had been initiated irreversibly in cells loaded with guanosine 5′-O-(3-thio-triphosphate) (GTP-[γS]). In contrast, when oscillations were initiated by loading cells with Ins(1,4,5)P 3, phorbol esters enhanced I K(Ca) without affecting the frequency of oscillation. The protein kinase inhibitor, staurosporine, reduced I K(Ca) without affecting [Ca2+]i and partially reversed the phorbol-ester-induced slowing of oscillation. Therefore, activation of PKC has two rapid effects on gonadotropes. It slows [Ca2+]i oscillations probably by actions on phospholipase C, and it enhances I K(Ca) probably by a direct action on the channels.

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Authors and Affiliations

  1. Department of Pharmacolog-y, 9-70 Medical Science Building, University of Alberta, T6G 2H7, Edmonton, Alberta, Canada

    Amy Tse & Frederick W. Tse

  2. Department of Physiology and Biophysics, SJ-40, G424 Health Sciences, University of Washington, 98195, Seattle, WA, USA

    Bertil Hille

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  1. Amy Tse
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  2. Frederick W. Tse
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  3. Bertil Hille
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Tse, A., Tse, F.W. & Hille, B. Modulation of Ca2+ oscillation and apamin-sensitive, Ca2+-activated K+ current in rat gonadotropes. Pflugers Arch. 430, 645–652 (1995). https://doi.org/10.1007/BF00386158

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  • DOI: https://doi.org/10.1007/BF00386158

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