{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:16:37Z","timestamp":1791342997477,"version":"4.3.1"},"reference-count":53,"publisher":"National Academy of Sciences","issue":"26","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[1999,12,21]]},"abstract":"<jats:p>\n                    The Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    -subunit is a voltage-gated, pore-forming membrane protein positioned at the intersection of two important lines of research: one exploring the diversity of Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channels and their physiological roles, and the other pursuing mechanisms of ataxia, dystonia, epilepsy, and migraine. \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    -Subunits are thought to support both P- and Q-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel currents, but the most direct test, a null mutant, has not been described, nor is it known which changes in neurotransmission might arise from elimination of the predominant Ca\n                    <jats:sup>2+<\/jats:sup>\n                    delivery system at excitatory nerve terminals. We generated \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    -deficient mice (\u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ) and found that they developed a rapidly progressive neurological deficit with specific characteristics of ataxia and dystonia before dying \u22483\u20134 weeks after birth. P-type currents in Purkinje neurons and P- and Q-type currents in cerebellar granule cells were eliminated completely whereas other Ca\n                    <jats:sup>2+<\/jats:sup>\n                    channel types, including those involved in triggering transmitter release, also underwent concomitant changes in density. Synaptic transmission in \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    hippocampal slices persisted despite the lack of P\/Q-type channels but showed enhanced reliance on N-type and R-type Ca\n                    <jats:sup>2+<\/jats:sup>\n                    entry. The \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice provide a starting point for unraveling neuropathological mechanisms of human diseases generated by mutations in \u03b1\n                    <jats:sub>1A<\/jats:sub>\n                    .\n                  <\/jats:p>","DOI":"10.1073\/pnas.96.26.15245","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:39:15Z","timestamp":1027679955000},"page":"15245-15250","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":405,"title":["Ablation of P\/Q-type Ca\n                    <sup>2+<\/sup>\n                    channel currents, altered synaptic transmission, and progressive ataxia in mice lacking the \u03b1\n                    <sub>1A<\/sub>\n                    -subunit"],"prefix":"10.1073","volume":"96","author":[{"given":"Kisun","family":"Jun","sequence":"first","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erika S.","family":"Piedras-Renter\u00eda","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephen M.","family":"Smith","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David B.","family":"Wheeler","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seong Beom","family":"Lee","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taehoon G.","family":"Lee","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hemin","family":"Chin","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael E.","family":"Adams","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard H.","family":"Scheller","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Richard W.","family":"Tsien","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hee-Sup","family":"Shin","sequence":"additional","affiliation":[{"name":"National Creative Research Initiatives Center for Calcium and Learning and Department of Life Science, Pohang University of Science and Technology, Pohang, Korea; Department of Molecular and Cellular Physiology and Howard Hughes Medical Institute, Stanford University School of Medicine, Stanford, CA 94305; Genetics Research Branch, Division of Neuroscience and Basic Behavioral Science, National Institutes of Health, Bethesda, MD 20892; and Departments of Entomology and Neuroscience, University of..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[1999,12,21]]},"reference":[{"key":"e_1_3_3_1_2","doi-asserted-by":"publisher","DOI":"10.1038\/350398a0"},{"key":"e_1_3_3_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0166-2236(95)80030-6"},{"key":"e_1_3_3_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4899-1775-1_2"},{"key":"e_1_3_3_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0143-4160(98)90055-0"},{"key":"e_1_3_3_5_2","first-page":"171","volume-title":"Calcium as a Cellular Regulator","author":"Wheeler D B","year":"1999","unstructured":"D B Wheeler, R W Tsien Calcium as a Cellular Regulator, eds E Carafoli, C Lee (Oxford Univ. 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