{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T09:05:09Z","timestamp":1791104709769,"version":"4.1.0"},"reference-count":28,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"published-print":{"date-parts":[[2014,1,15]]},"abstract":"<jats:p> Recent reports have noted that T-type Ca<jats:sup>2+<\/jats:sup> channels (Ca<jats:sub>V<\/jats:sub>3.x) are expressed in vascular smooth muscle and are potential targets of regulation. In this study, we examined whether and by what mechanism nitric oxide (NO), a key vasodilator, influences this conductance. Using patch-clamp electrophysiology and rat cerebral arterial smooth muscle cells, we monitored an inward Ba<jats:sup>2+<\/jats:sup> current that was divisible into a nifedipine-sensitive and -insensitive component. The latter was abolished by T-type channel blocker and displayed classic T-type properties including faster activation and steady-state inactivation at hyperpolarized potentials. NO donors (sodium nitroprusside, S-nitroso- N-acetyl- dl-penicillamine), along with activators of protein kinase G (PKG) signaling, suppressed T-type currents. Inhibitors of guanylyl cyclase\/PKG {1H-[1,2,4]oxadiazolo[4,3-a]quinoxalin-1-one (ODQ) and KT5823, respectively}, had no effect on basal currents; KT5823 did, however, mask T-type Ca<jats:sup>2+<\/jats:sup> channel current inhibition by NO\/PKG. Functional experiments confirmed an inhibitory effect for NO on the T-type contribution to cerebral arterial myogenic tone. Cumulatively, our findings support the view that T-type Ca<jats:sup>2+<\/jats:sup> channels are a regulatory target of vasodilatory signaling pathways. This targeting will influence Ca<jats:sup>2+<\/jats:sup> dynamics and consequent tone development in the cerebral circulation. <\/jats:p>","DOI":"10.1152\/ajpheart.00743.2013","type":"journal-article","created":{"date-parts":[[2013,11,16]],"date-time":"2013-11-16T06:01:47Z","timestamp":1384581707000},"page":"H279-H285","source":"Crossref","is-referenced-by-count":42,"title":["Nitric oxide suppresses vascular voltage-gated T-type Ca<sup>2+<\/sup> channels through cGMP\/PKG signaling"],"prefix":"10.1152","volume":"306","author":[{"given":"Osama F.","family":"Harraz","sequence":"first","affiliation":[{"name":"Hotchkiss Brain and Libin Cardiovascular Institutes and Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; and"},{"name":"Department of Pharmacology and Toxicology, Faculty of Pharmacy, Alexandria University, Egypt"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Suzanne E.","family":"Brett","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain and Libin Cardiovascular Institutes and Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Donald G.","family":"Welsh","sequence":"additional","affiliation":[{"name":"Hotchkiss Brain and Libin Cardiovascular Institutes and Department of Physiology and Pharmacology, University of Calgary, Alberta, Canada; and"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"24","reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00476.2012"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00460.2011"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.203620"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.56.2.205"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.112.277145"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1016\/j.abb.2011.02.024"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000147311.54833.03"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajprenal.00042.2005"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1038\/nn1779"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1038\/288373a0"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1023\/A:1018616814417"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1242\/jcs.128363"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1111\/micc.12038"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvt043"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.199br.x"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1111\/j.1469-7793.1998.211br.x"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1038\/jcbfm.2010.11"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-013-8493-8"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0039965"},{"key":"B20","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M705478200"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2006.126128"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00018.2002"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00490.2012"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1038\/ki.2010.429"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1172\/JCI119146"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1111\/j.1476-5381.2012.02174.x"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1161\/hh0302.105662"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2012.08.032"}],"container-title":["American Journal of Physiology-Heart and Circulatory Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.physiology.org\/doi\/pdf\/10.1152\/ajpheart.00743.2013","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,9,8]],"date-time":"2019-09-08T21:54:17Z","timestamp":1567979657000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.physiology.org\/doi\/10.1152\/ajpheart.00743.2013"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2014,1,15]]},"references-count":28,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2014,1,15]]}},"alternative-id":["10.1152\/ajpheart.00743.2013"],"URL":"https:\/\/doi.org\/10.1152\/ajpheart.00743.2013","relation":{},"ISSN":["0363-6135","1522-1539"],"issn-type":[{"value":"0363-6135","type":"print"},{"value":"1522-1539","type":"electronic"}],"subject":[],"published":{"date-parts":[[2014,1,15]]}}}