{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T07:31:59Z","timestamp":1778830319169,"version":"3.51.4"},"reference-count":60,"publisher":"Wiley","issue":"21","license":[{"start":{"date-parts":[[2015,10,1]],"date-time":"2015-10-01T00:00:00Z","timestamp":1443657600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"name":"Consejer\u00eda de Innovaci\u00f3n y Ciencia de la Junta de Andaluc\u00eda","award":["P11-CTS-7045"],"award-info":[{"award-number":["P11-CTS-7045"]}]},{"DOI":"10.13039\/501100004837","name":"Spanish Ministry of Science and Innovation","doi-asserted-by":"crossref","award":["SAF2010-17694"],"award-info":[{"award-number":["SAF2010-17694"]}],"id":[{"id":"10.13039\/501100004837","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2015,11]]},"abstract":"<jats:sec><jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"bullet\">\n<jats:list-item><jats:p>T\u2010type Ca<jats:sup>2+<\/jats:sup> channels are expressed in the ventricular myocytes of the fetal and perinatal heart, but are downregulated as development progresses. However, these channels are re\u2010expressed in adult cardiomyocytes under pathological conditions.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Hypoxia induces the upregulation of the T\u2010type Ca<jats:sup>2+<\/jats:sup> channel Ca<jats:sub>v<\/jats:sub>3.2 mRNA in cardiac myocytes, whereas Ca<jats:sub>v<\/jats:sub>3.1 mRNA is not significantly altered.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>The effect of hypoxia on Ca<jats:sub>v<\/jats:sub>3.2 mRNA requires hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1) stabilization and involves the small monomeric G\u2010protein RhoA and its effector ROCKI.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Our results suggest that the hypoxic regulation of the Ca<jats:sub>v<\/jats:sub>3.2 channels may be involved in the increased probability of developing arrhythmias observed in ischemic situations, and in the pathogenesis of diseases associated with hypoxic Ca<jats:sup>2+<\/jats:sup> overload.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><\/jats:sec><jats:sec><jats:title>Abstract<\/jats:title><jats:p>T\u2010type Ca<jats:sup>2+<\/jats:sup> channels are expressed in the ventricular myocytes of the fetal and perinatal heart, but are normally downregulated as development progresses. Interestingly, however, these channels are re\u2010expressed in adult cardiomyocytes under pathological conditions. We investigated low voltage\u2010activated T\u2010type Ca<jats:sup>2+<\/jats:sup> channel regulation in hypoxia in rat cardiomyocytes. Molecular studies revealed that hypoxia induces the upregulation of Ca<jats:sub>v<\/jats:sub>3.2\u00a0mRNA, whereas Ca<jats:sub>v<\/jats:sub>3.1 mRNA is not significantly altered. The effect of hypoxia on Ca<jats:sub>v<\/jats:sub>3.2\u00a0mRNA was time\u2010 and dose\u2010dependent, and required hypoxia inducible factor\u20101\u03b1 (HIF\u20101\u03b1) stabilization. Patch\u2010clamp recordings confirmed that T\u2010type Ca<jats:sup>2+<\/jats:sup> channel currents were upregulated in hypoxic conditions, and the addition of 50\u00a0\u03bc<jats:sc>m<\/jats:sc> NiCl<jats:sub>2<\/jats:sub> (a T\u2010type channel blocker) demonstrated that the Ca<jats:sub>v<\/jats:sub>3.2 channel is responsible for this upregulation. This increase in current density was not accompanied by significant changes in the Ca<jats:sub>v<\/jats:sub>3.2 channel electrophysiological properties. The small monomeric G\u2010protein RhoA and its effector Rho\u2010associated kinase I (ROCKI), which are known to play important roles in cardiovascular physiology, were also upregulated in neonatal rat ventricular myocytes subjected to hypoxia. Pharmacological experiments indicated that both proteins were involved in the observed upregulation of the Ca<jats:sub>v<\/jats:sub>3.2 channel and the stabilization of HIF\u20101\u03b1 that occurred in response to hypoxia. These results suggest a possible role for Ca<jats:sub>v<\/jats:sub>3.2 channels in the increased probability of developing arrhythmias observed in ischaemic situations, and in the pathogenesis of diseases associated with hypoxic Ca<jats:sup>2+<\/jats:sup> overload.<\/jats:p><\/jats:sec>","DOI":"10.1113\/jp271053","type":"journal-article","created":{"date-parts":[[2015,9,2]],"date-time":"2015-09-02T17:41:43Z","timestamp":1441215703000},"page":"4729-4745","source":"Crossref","is-referenced-by-count":24,"title":["Hypoxic induction of T\u2010type Ca<sup>2+<\/sup> channels in rat cardiac myocytes: role of HIF\u20101\u03b1 and RhoA\/ROCK signalling"],"prefix":"10.1113","volume":"593","author":[{"given":"P.","family":"Gonz\u00e1lez\u2010Rodr\u00edguez","sequence":"first","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad de Sevilla  Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"D.","family":"Falc\u00f3n","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad de Sevilla  Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"M. J.","family":"Castro","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"Ure\u00f1a","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad de Sevilla  Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"J.","family":"L\u00f3pez\u2010Barneo","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad de Sevilla  Sevilla Spain"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"A.","family":"Castellano","sequence":"additional","affiliation":[{"name":"Instituto de Biomedicina de Sevilla (IBiS) Hospital Universitario Virgen del Roc\u00edo\/CSIC\/Universidad de Sevilla  Sevilla Spain"},{"name":"Departamento de Fisiolog\u00eda M\u00e9dica y Biof\u00edsica, Facultad de Medicina Universidad de Sevilla  Sevilla 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