{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:05:02Z","timestamp":1791104702298,"version":"4.1.0"},"reference-count":37,"publisher":"Rockefeller University Press","issue":"3","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,9,1]]},"abstract":"<jats:p>Plasma membrane large-conductance Ca2+-activated K+ (BKCa) channels and sarcoplasmic reticulum inositol 1,4,5-trisphosphate (IP3) receptors (IP3Rs) are expressed in a wide variety of cell types, including arterial smooth muscle cells. Here, we studied BKCa channel regulation by IP3 and IP3Rs in rat and mouse cerebral artery smooth muscle cells. IP3 activated BKCa channels both in intact cells and in excised inside-out membrane patches. IP3 caused concentration-dependent BKCa channel activation with an apparent dissociation constant (Kd) of \u223c4 \u00b5M at physiological voltage (\u221240 mV) and intracellular Ca2+ concentration ([Ca2+]i; 10 \u00b5M). IP3 also caused a leftward-shift in BKCa channel apparent Ca2+ sensitivity and reduced the Kd for free [Ca2+]i from \u223c20 to 12 \u00b5M, but did not alter the slope or maximal Po. BAPTA, a fast Ca2+ buffer, or an elevation in extracellular Ca2+ concentration did not alter IP3-induced BKCa channel activation. Heparin, an IP3R inhibitor, and a monoclonal type 1 IP3R (IP3R1) antibody blocked IP3-induced BKCa channel activation. Adenophostin A, an IP3R agonist, also activated BKCa channels. IP3 activated BKCa channels in inside-out patches from wild-type (IP3R1+\/+) mouse arterial smooth muscle cells, but had no effect on BKCa channels of IP3R1-deficient (IP3R1\u2212\/\u2212) mice. Immunofluorescence resonance energy transfer microscopy indicated that IP3R1 is located in close spatial proximity to BKCa \u03b1 subunits. The IP3R1 monoclonal antibody coimmunoprecipitated IP3R1 and BKCa channel \u03b1 and \u03b21 subunits from cerebral arteries. In summary, data indicate that IP3R1 activation elevates BKCa channel apparent Ca2+ sensitivity through local molecular coupling in arterial smooth muscle cells.<\/jats:p>","DOI":"10.1085\/jgp.201010453","type":"journal-article","created":{"date-parts":[[2010,8,17]],"date-time":"2010-08-17T04:12:09Z","timestamp":1282018329000},"page":"283-291","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":59,"title":["Type 1 IP3 receptors activate BKCa channels via local molecular coupling in arterial smooth muscle cells"],"prefix":"10.1085","volume":"136","author":[{"given":"Guiling","family":"Zhao","sequence":"first","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zachary P.","family":"Neeb","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"M. Dennis","family":"Leo","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Judith","family":"Pachuau","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adebowale","family":"Adebiyi","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kunfu","family":"Ouyang","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 92093 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ju","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Medicine, University of California, San Diego, La Jolla, CA 92093 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jonathan H.","family":"Jaggar","sequence":"additional","affiliation":[{"name":"Department of Physiology, University of Tennessee Health Science Center, Memphis, TN 38163 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,8,16]]},"reference":[{"key":"2023072622121572500_bib1","doi-asserted-by":"publisher","first-page":"1603","DOI":"10.1161\/CIRCRESAHA.110.216804","article-title":"Isoform-selective physical coupling of TRPC3 channels to IP3 receptors in smooth muscle cells regulates arterial contractility","volume":"106","author":"Adebiyi","year":"2010","journal-title":"Circ. 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