{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T06:27:42Z","timestamp":1787120862331,"version":"build-2736575974"},"reference-count":45,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T00:00:00Z","timestamp":1787097600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","award":["R01 ES025229, T32 HL086350, T32 ES007059"],"award-info":[{"award-number":["R01 ES025229, T32 HL086350, T32 ES007059"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Physiol."],"abstract":"<jats:sec>\n                    <jats:title>Background<\/jats:title>\n                    <jats:p>Despite the decline in secondhand smoke (SHS) exposure since the implementation of smoking bans in public places, SHS exposure remains a significant health risk factor affecting about 1\/3 of non-smokers worldwide. We previously showed that 12 weeks of SHS exposure reduces heart rate variability, an effect that peaks at week 4. We further showed that 4 weeks of SHS exposure significantly reduces cardiac vagal neuron\u2019s (CVN) excitability that is associated with a reduced small conductance calcium-dependent potassium (SK) channel activity.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Objectives<\/jats:title>\n                    <jats:p>This study aimed to test whether the reduced excitability in CVNs also wanes with longer exposure duration (12 weeks) and whether 4-aminopyridine sensitive voltage-gated potassium channels contribute to the SHS-induced decreases in neuronal excitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Adult male mice were exposed to 12 weeks of filtered air or SHS at an environmental-relevant concentration (3 mg\/m\n                      <jats:sup>3<\/jats:sup>\n                      , 6 hr\/d, 5d\/wk). We performed whole-cell patch-clamp recordings on anatomically identified CVNs in the nucleus ambiguus.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>12 weeks of SHS exposure significantly increased action potential (AP) thresholds and reduced spiking responses to excitation. SHS exposure did not significantly alter resting membrane potential, or 4-aminopyridine sensitive channel activity, suggesting that leak potassium channels and voltage gated potassium channels were unlikely to contribute to the reduced excitability. We found two adaptations that may serve to counteract the reduced excitability. First, APs inactivated at higher voltages that helped to maintain the spiking response range and increase maximum discharge frequency. Second, blocking SK channels with apamin had smaller effects on the spiking response in CVNs from SHS-exposed mice, suggesting that a reduced SK channel activation during spiking activity may help to dampen the reduced excitability.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>Environmentally relevant SHS exposure reduces neuronal excitability of CVNs through mechanisms other than enhanced SK and voltage-gated potassium channel functions.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fphys.2026.1907874","type":"journal-article","created":{"date-parts":[[2026,8,19]],"date-time":"2026-08-19T05:46:55Z","timestamp":1787118415000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":0,"title":["Extended secondhand smoke exposure alters potassium channel activity and reduces excitability of cardiac vagal neurons in mice"],"prefix":"10.3389","volume":"17","author":[{"given":"Junqing","family":"Sun","sequence":"first","affiliation":[{"name":"Department of Pharmacology, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Shiyue","family":"Pan","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emma","family":"Karey","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kent E.","family":"Pinkerton","sequence":"additional","affiliation":[{"name":"Center for Health and the Environment, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chao-Yin","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, University of California, Davis","place":["Davis, CA, United States"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2026,8,19]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"320","DOI":"10.1016\/0006-8993(92)90833-u","article-title":"Electrical stimulation of nucleus tractus solitarius excites vagal preganglionic cardiomotor neurons of the nucleus ambiguus in rats","volume":"574","author":"Agarwal","year":"1992","journal-title":"Brain Res."},{"key":"B2","doi-asserted-by":"publisher","first-page":"2684","DOI":"10.1161\/CIRCULATIONAHA.104.492215","article-title":"Cardiovascular effects of secondhand smoke: nearly as large as smoking","volume":"111","author":"Barnoya","year":"2005","journal-title":"Circulation"},{"key":"B3","doi-asserted-by":"publisher","first-page":"370","DOI":"10.1111\/j.1749-6632.1999.tb11298.x","article-title":"Small-conductance calcium-activated potassium channels","volume":"868","author":"Bond","year":"1999","journal-title":"Ann. 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