{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,7]],"date-time":"2026-10-07T03:07:24Z","timestamp":1791342444263,"version":"4.3.1"},"reference-count":41,"publisher":"Wiley","issue":"4","license":[{"start":{"date-parts":[[2014,1,24]],"date-time":"2014-01-24T00:00:00Z","timestamp":1390521600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Dutch National Epilepsy Foundation","award":["06-13"],"award-info":[{"award-number":["06-13"]}]},{"name":"\u2018Platform alternatief voor dierproeven\u2019","award":["114000091"],"award-info":[{"award-number":["114000091"]}]}],"content-domain":{"domain":["bpspubs.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["British J Pharmacology"],"published-print":{"date-parts":[[2014,2]]},"abstract":"<jats:sec>\n                    <jats:title>Background and purpose<\/jats:title>\n                    <jats:p>\n                      Voltage\u2010activated\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:roman>\n                          Na\n                          <jats:sup>+<\/jats:sup>\n                        <\/jats:roman>\n                      <\/jats:styled-content>\n                      channels contain one distinct \u03b1\u2010subunit. In the brain\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.1,\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.2,\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.3 and\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.6 are the four most abundantly expressed \u03b1\u2010subunits. The antiepileptic drugs (\n                      <jats:styled-content style=\"fixed-case\">AEDs<\/jats:styled-content>\n                      ) carbamazepine, phenytoin and lamotrigine have voltage\u2010gated\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:roman>\n                          Na\n                          <jats:sup>+<\/jats:sup>\n                        <\/jats:roman>\n                      <\/jats:styled-content>\n                      channels as their primary therapeutic targets. This study provides a systematic comparison of the biophysical properties of these four \u03b1\u2010subunits and characterizes their interaction with carbamazepine, phenytoin and lamotrigine.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Experimental approach<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:roman>\n                          Na\n                          <jats:sup>+<\/jats:sup>\n                        <\/jats:roman>\n                      <\/jats:styled-content>\n                      currents were recorded in voltage\u2010clamp mode in\n                      <jats:styled-content style=\"fixed-case\">HEK293<\/jats:styled-content>\n                      cells stably expressing one of the four \u03b1\u2010subunits.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Key results<\/jats:title>\n                    <jats:p>\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.2 and\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.3 subunits have a relatively slow recovery from inactivation, compared with the other subunits and\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.1 subunits generate the largest window current. Lamotrigine evokes a larger maximal shift of the steady\u2010state inactivation relationship than carbamazepine or phenytoin. Carbamazepine shows the highest binding rate to the \u03b1\u2010subunits. Lamotrigine binding to\n                      <jats:styled-content style=\"fixed-case\">\n                        Na\n                        <jats:sub>V<\/jats:sub>\n                      <\/jats:styled-content>\n                      1.1 subunits is faster than to the other \u03b1\u2010subunits. Lamotrigine unbinding from the \u03b1\u2010subunits is slower than that of carbamazepine and phenytoin.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions and implications<\/jats:title>\n                    <jats:p>\n                      The four\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:roman>\n                          Na\n                          <jats:sup>+<\/jats:sup>\n                        <\/jats:roman>\n                      <\/jats:styled-content>\n                      channel \u03b1\u2010subunits show subtle differences in their biophysical properties, which, in combination with their (sub)cellular expression patterns in the brain, could contribute to differences in neuronal excitability. We also observed differences in the parameters that characterize\n                      <jats:styled-content style=\"fixed-case\">AED<\/jats:styled-content>\n                      binding to the\n                      <jats:styled-content style=\"fixed-case\">\n                        <jats:roman>\n                          Na\n                          <jats:sup>+<\/jats:sup>\n                        <\/jats:roman>\n                      <\/jats:styled-content>\n                      channel subunits. Particularly, lamotrigine binding to the four \u03b1\u2010subunits suggests a subunit\u2010specific response. Such differences will have consequences for the clinical efficacy of\n                      <jats:styled-content style=\"fixed-case\">AEDs<\/jats:styled-content>\n                      . Knowledge of the biophysical and binding parameters could be employed to optimize therapeutic strategies and drug development.\n                    <\/jats:p>\n                  <\/jats:sec>","DOI":"10.1111\/bph.12534","type":"journal-article","created":{"date-parts":[[2013,11,28]],"date-time":"2013-11-28T00:04:54Z","timestamp":1385597094000},"page":"1054-1067","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":67,"title":["Properties of human brain sodium channel \u03b1\u2010subunits expressed in\n                    <scp>HEK293<\/scp>\n                    cells and their modulation by carbamazepine, phenytoin and lamotrigine"],"prefix":"10.1111","volume":"171","author":[{"given":"Xin","family":"Qiao","sequence":"first","affiliation":[{"name":"Center for NeuroScience Swammerdam Institute for Life Sciences University of Amsterdam Amsterdam The 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