{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,23]],"date-time":"2026-09-23T12:22:32Z","timestamp":1790166152716,"version":"4.1.0"},"reference-count":38,"publisher":"National Academy of Sciences","issue":"48","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2011,11,29]]},"abstract":"<jats:p>\n                    The voltage-gated sodium channel Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 is known to function in the transmission of pain signals induced by cold, heat, and mechanical stimuli. Sequence variants of human Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 have been linked to altered cardiac conduction. We identified an allele of\n                    <jats:italic>Scn10a<\/jats:italic>\n                    encoding the \u03b1-subunit of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 among mice homozygous for\n                    <jats:italic>N<\/jats:italic>\n                    -ethyl-\n                    <jats:italic>N<\/jats:italic>\n                    -nitrosourea-induced mutations. The allele creates a dominant neurobehavioral phenotype termed\n                    <jats:italic>Possum<\/jats:italic>\n                    , characterized by transient whole-body tonic immobility induced by pinching the skin at the back of the neck (\u201cscruffing\u201d). The\n                    <jats:italic>Possum<\/jats:italic>\n                    mutation enhanced Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 sodium currents and neuronal excitability and heightened sensitivity of mutants to cold stimuli. Striking electroencephalographic changes were observed concomitant with the scruffing-induced behavioral change. In addition, electrocardiography demonstrated that\n                    <jats:italic>Possum<\/jats:italic>\n                    mice exhibited marked sinus bradycardia and R-R variability upon scruffing, abrogated by infusion of atropine. However, atropine failed to prevent or mitigate the tonic immobility response. Hyperactive sodium conduction via Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 thus leads to a complex neurobehavioral phenotype, which resembles catatonia in schizophrenic humans and tonic immobility in other mammals upon application of a discrete stimulus; no other form of mechanosensory stimulus could induce the immobility phenotype. Our data confirm the involvement of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 in transducing pain initiated by cold and additionally implicate Na\n                    <jats:sub>v<\/jats:sub>\n                    1.8 in previously unknown functions in the central nervous system and heart.\n                  <\/jats:p>","DOI":"10.1073\/pnas.1117020108","type":"journal-article","created":{"date-parts":[[2011,11,16]],"date-time":"2011-11-16T10:01:19Z","timestamp":1321437679000},"page":"19413-19418","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":46,"title":["Hypermorphic mutation of the voltage-gated sodium channel encoding gene\n                    <i>Scn10a<\/i>\n                    causes a dramatic stimulus-dependent neurobehavioral phenotype"],"prefix":"10.1073","volume":"108","author":[{"given":"Amanda L.","family":"Blasius","sequence":"first","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Adrienne E.","family":"Dubin","sequence":"additional","affiliation":[{"name":"Cell Biology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matt J.","family":"Petrus","sequence":"additional","affiliation":[{"name":"Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Byung-Kwan","family":"Lim","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of California at San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anna","family":"Narezkina","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of California at San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jos\u00e9 R.","family":"Criado","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Neurosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Derek N.","family":"Wills","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Neurosciences, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yu","family":"Xia","sequence":"additional","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Eva Marie Y.","family":"Moresco","sequence":"additional","affiliation":[{"name":"Departments of aGenetics,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cindy","family":"Ehlers","sequence":"additional","affiliation":[{"name":"Molecular and Integrative Neurosciences, and"},{"name":"Molecular and Experimental Medicine, The Scripps Research Institute, La Jolla, CA 92037;"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kirk U.","family":"Knowlton","sequence":"additional","affiliation":[{"name":"Department of Medicine, Division of Cardiology, University of California at San Diego, La Jolla, CA 92093"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ardem","family":"Patapoutian","sequence":"additional","affiliation":[{"name":"Cell Biology,"},{"name":"Genomics Institute of the Novartis Research Foundation, San Diego, CA 92121; 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