{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T08:16:54Z","timestamp":1791274614179,"version":"4.1.0"},"reference-count":47,"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":[[2001,12,18]]},"abstract":"<jats:p>\n                    Inactivation is a fundamental characteristic of Na\n                    <jats:sup>+<\/jats:sup>\n                    channels, and small changes cause skeletal muscle paralysis and\n myotonia, epilepsy, and cardiac arrhythmia. Brain\n Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a channels have faster inactivation than cardiac\n Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 channels, but minor differences in inactivation gate\n structure are not responsible. We constructed chimeras in which the C\n termini beyond the fourth homologous domains of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a and\n Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 were exchanged. Replacing the C-terminal domain (CT)\n of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a with that of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5\n (Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2\/1.5CT) slowed inactivation at +40 mV \u22482-fold,\n making it similar to Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5. Conversely, replacing the CT\n of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 with that of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a (Nav1.5\/1.2CT)\n accelerated inactivation, making it similar to Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a.\n Activation properties were unaffected. The voltage dependence of\n steady-state inactivation of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 is 16 mV more negative\n than that of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a. The steady-state inactivation curve\n of Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2a was shifted +12 mV in\n Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2\/1.5CT, consistent with destabilization of the\n inactivated state. Conversely, Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5\/1.2CT was shifted\n \u221214 mV relative to Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5, consistent with stabilization\n of the inactivated state. Although these effects of exchanging C\n termini were consistent with their effects on inactivation kinetics,\n they magnified the differences in the voltage dependence of\n inactivation between brain and cardiac channels rather than\n transferring them. Thus, other parts of these channels determine the\n basal difference in steady-state inactivation. Deletion of the distal\n half of either the Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2 or Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 CTs\n accelerated open-state inactivation and negatively shifted steady-state\n inactivation. Thus, the C terminus has a strong influence on kinetics\n and voltage dependence of inactivation in brain\n Na\n                    <jats:sub>v<\/jats:sub>\n                    1.2 and cardiac Na\n                    <jats:sub>v<\/jats:sub>\n                    1.5 channels and is\n primarily responsible for their differing rates of channel\n inactivation.\n                  <\/jats:p>","DOI":"10.1073\/pnas.211563298","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:36:44Z","timestamp":1027679804000},"page":"15348-15353","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":123,"title":["Role of the C-terminal domain in inactivation of brain and cardiac sodium channels"],"prefix":"10.1073","volume":"98","author":[{"given":"Massimo","family":"Mantegazza","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of Washington, Seattle, WA\r 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