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These Nav channels exhibit unique biophysical properties tailored to their specific cellular environments. Here, we explore the interactions between Nav channel availability and resting membrane potential across a spectrum of cell types, including inhibitory GABAergic neurons, excitatory glutamatergic neurons, skeletal muscles, cardiomyocytes and dorsal root ganglion neurons. We highlight how these interactions, modulated by post\u2010translational modifications and in relation to spatial localizations, are critical for maintaining physiological function and how even small shifts in channel properties can have significant pathophysiological consequences. In addition, we discuss the implications for drug discovery, emphasizing the need to consider the native cellular environment in developing Nav\u2010targeting therapies. This perspective provides a framework for understanding the nuanced role of Nav channels in health and disease.\n                    <jats:boxed-text content-type=\"graphic\" position=\"anchor\">\n                      <jats:graphic xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" mimetype=\"image\/png\" position=\"anchor\" specific-use=\"enlarged-web-image\" xlink:href=\"graphic\/tjp70515-gra-0001-m.png\">\n                        <jats:alt-text>image<\/jats:alt-text>\n                      <\/jats:graphic>\n                    <\/jats:boxed-text>\n                  <\/jats:p>","DOI":"10.1113\/jp290383","type":"journal-article","created":{"date-parts":[[2026,4,2]],"date-time":"2026-04-02T05:12:16Z","timestamp":1775106736000},"page":"3738-3762","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Matching sodium channel availability to resting membrane potential: Biophysical logic across excitable cell types"],"prefix":"10.1113","volume":"604","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2171-0744","authenticated-orcid":false,"given":"Mohammad\u2010Reza","family":"Ghovanloo","sequence":"first","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven CT USA"},{"name":"Center for Neuroscience &amp; Regeneration Research Yale University  West Haven CT USA"},{"name":"Neuro\u2010Rehabilitation Research Center Veterans Affairs Connecticut Healthcare System  West Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5718-7177","authenticated-orcid":false,"given":"Stephen G.","family":"Waxman","sequence":"additional","affiliation":[{"name":"Department of Neurology Yale School of Medicine  New Haven CT USA"},{"name":"Center for Neuroscience &amp; Regeneration Research Yale University  West Haven CT USA"},{"name":"Neuro\u2010Rehabilitation Research Center Veterans Affairs Connecticut Healthcare System  West Haven CT USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,4,1]]},"reference":[{"key":"e_1_2_2_2_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP274536"},{"key":"e_1_2_2_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/JP270139"},{"key":"e_1_2_2_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1974.sp010620"},{"key":"e_1_2_2_5_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.aac5464"},{"key":"e_1_2_2_6_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jjcc.2019.01.009"},{"key":"e_1_2_2_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/bph.70231"},{"key":"e_1_2_2_8_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41582-020-00415-2"},{"key":"e_1_2_2_9_1","doi-asserted-by":"publisher","DOI":"10.1093\/brain\/awf037"},{"key":"e_1_2_2_10_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.19-19-08589.1999"},{"key":"e_1_2_2_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2021.108745"},{"key":"e_1_2_2_12_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.2003.00373.x"},{"key":"e_1_2_2_13_1","doi-asserted-by":"publisher","DOI":"10.3390\/life13051191"},{"key":"e_1_2_2_14_1","doi-asserted-by":"publisher","DOI":"10.1085\/jgp.81.5.613"},{"key":"e_1_2_2_15_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00052.2017"},{"key":"e_1_2_2_16_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.adj9173"},{"key":"e_1_2_2_17_1","doi-asserted-by":"publisher","DOI":"10.1002\/ana.21527"},{"key":"e_1_2_2_18_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.23-32-10338.2003"},{"key":"e_1_2_2_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_48"},{"key":"e_1_2_2_20_1","doi-asserted-by":"publisher","DOI":"10.1007\/s10557-012-6421-1"},{"key":"e_1_2_2_21_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.090034797"},{"key":"e_1_2_2_22_1","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.neuro.29.051605.112815"},{"key":"e_1_2_2_23_1","doi-asserted-by":"publisher","DOI":"10.1007\/164_2017_52"},{"key":"e_1_2_2_24_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-3495(93)81045-2"},{"key":"e_1_2_2_25_1","doi-asserted-by":"publisher","DOI":"10.1126\/scitranslmed.aad7653"},{"key":"e_1_2_2_26_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1528-1167.2010.02845.x"},{"key":"e_1_2_2_27_1","doi-asserted-by":"publisher","DOI":"10.1080\/19336950.2023.2281714"},{"key":"e_1_2_2_28_1","doi-asserted-by":"crossref","unstructured":"Catterall W. 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