{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T14:23:03Z","timestamp":1790518983044,"version":"4.1.0"},"reference-count":46,"publisher":"Rockefeller University Press","issue":"6","content-domain":{"domain":["rupress.org"],"crossmark-restriction":true},"short-container-title":[],"published-print":{"date-parts":[[2010,6,1]]},"abstract":"<jats:p>Bidirectional communication between the 1,4-dihydropyridine receptor (DHPR) in the plasma membrane and the type 1 ryanodine receptor (RYR1) in the sarcoplasmic reticulum (SR) is responsible for both skeletal-type excitation\u2013contraction coupling (voltage-gated Ca2+ release from the SR) and increased amplitude of L-type Ca2+ current via the DHPR. Because the DHPR and RYR1 are functionally coupled, mutations in RYR1 that are linked to malignant hyperthermia (MH) may affect DHPR activity. For this reason, we investigated whether cultured myotubes originating from mice carrying an MH-linked mutation in RYR1 (R163C) had altered voltage-gated Ca2+ release from the SR, membrane-bound charge movement, and\/or L-type Ca2+ current. In myotubes homozygous (Hom) for the R163C mutation, voltage-gated Ca2+ release from the SR was substantially reduced and shifted (\u223c10 mV) to more hyperpolarizing potentials compared with wild-type (WT) myotubes. Intramembrane charge movements of both Hom and heterozygous (Het) myotubes displayed hyperpolarizing shifts similar to that observed in voltage-gated SR Ca2+ release. The current\u2013voltage relationships for L-type currents in both Hom and Het myotubes were also shifted to more hyperpolarizing potentials (\u223c7 and 5 mV, respectively). Compared with WT myotubes, Het and Hom myotubes both displayed a greater sensitivity to the L-type channel agonist \u00b1Bay K 8644 (10 \u00b5M). In general, L-type currents in WT, Het, and Hom myotubes inactivated modestly after 30-s prepulses to \u221250, \u221210, 0, 10, 20, and 30 mV. However, L-type currents in Hom myotubes displayed a hyperpolarizing shift in inactivation relative to L-type currents in either WT or Het myotubes. Our present results indicate that mutations in RYR1 can alter DHPR activity and raise the possibility that this altered DHPR function may contribute to MH episodes.<\/jats:p>","DOI":"10.1085\/jgp.200910329","type":"journal-article","created":{"date-parts":[[2010,5,18]],"date-time":"2010-05-18T03:25:27Z","timestamp":1274153127000},"page":"629-640","update-policy":"https:\/\/doi.org\/10.1085\/jgp.crossmarkpolicy","source":"Crossref","is-referenced-by-count":24,"title":["A malignant hyperthermia\u2013inducing mutation in RYR1 (R163C): consequent alterations in the functional properties of DHPR channels"],"prefix":"10.1085","volume":"135","author":[{"given":"Roger A.","family":"Bannister","sequence":"first","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO 80045 1"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eric","family":"Est\u00e8ve","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115 2"},{"name":"Universit\u00e9 Victor Segalen Bordeaux 2, Institut National de la Sant\u00e9 et de la Recherche Medicale U885, Laboratoire de Physiologie Cellulaire Respiratoire, 33076 Bordeaux, France 3"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 M.","family":"Eltit","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115 2"},{"name":"Programa de Biologia Molecular y Celular, Instituto de Ciencias Biomedicas Faculdad de Medicina, Universidad de Chile, Casilla 70005, Santiago, Chile 4"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Isaac N.","family":"Pessah","sequence":"additional","affiliation":[{"name":"Department of Molecular Biosciences, School of Veterinary Medicine, University of California, Davis, Davis, CA 95616 5"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul D.","family":"Allen","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"L\u00f3pez","sequence":"additional","affiliation":[{"name":"Department of Anesthesiology Perioperative and Pain Medicine, Brigham and Women\u2019s Hospital, Boston, MA 02115 2"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kurt G.","family":"Beam","sequence":"additional","affiliation":[{"name":"Department of Physiology and Biophysics, School of Medicine, University of Colorado-Anschutz Medical Campus, Aurora, CO 80045 1"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"291","published-online":{"date-parts":[[2010,5,17]]},"reference":[{"key":"2023072621594545700_bib1","doi-asserted-by":"publisher","first-page":"429","DOI":"10.1085\/jgp.94.3.429","article-title":"A novel calcium current in dysgenic skeletal muscle","volume":"94","author":"Adams","year":"1989","journal-title":"J. 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