{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,12]],"date-time":"2026-07-12T19:11:40Z","timestamp":1783883500827,"version":"3.55.0"},"reference-count":50,"publisher":"American Physiological Society","issue":"2","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Regulatory, Integrative and Comparative Physiology"],"published-print":{"date-parts":[[2014,7,15]]},"abstract":"<jats:p>We determined the contribution of vascular large conductance Ca<jats:sup>2+<\/jats:sup>-activated K<jats:sup>+<\/jats:sup>(BK) and L-type Ca<jats:sup>2+<\/jats:sup>channel dysregulation to exaggerated mortality in cecal ligation\/puncture (CLP)-induced septic BK channel \u03b21-subunit knockout (BK \u03b21-KO, smooth muscle specific) mice. CLP-induced hemodynamic changes and mortality were assessed over 7 days in wild-type (WT) and BK \u03b21-KO mice that were either untreated, given volume resuscitation (saline), or saline + calcium channel blocker nicardipine. Some mice were euthanized 24 h post-CLP to measure tissue injury and vascular and immune responses. CLP-induced hypotension was similar in untreated WT and BK \u03b21-KO mice, but BK \u03b21-KO mice died sooner. At 24 h post-CLP (mortality latency in BK \u03b21-KO mice), untreated CLP-BK \u03b21-KO mice showed more severe hypothermia, lower tissue perfusion, polymorphonuclear neutrophil infiltration-independent severe intestinal necrosis, and higher serum cytokine levels than CLP-WT mice. Saline resuscitation improved survival in CLP-WT but not CLP-BK \u03b21-KO mice. Saline + nicardipine-treated CLP-BK \u03b21-KO mice exhibited longer survival times, higher tissue perfusion, less intestinal injury, and lower cytokines versus untreated CLP-BK \u03b21-KO mice. These improvements were absent in treated CLP-WT mice, although saline + nicardipine improved blood pressure similarly in both septic mice. At 24 h post-CLP, BK and L-type Ca<jats:sup>2+<\/jats:sup>channel functions in vitro were maintained in mesenteric arteries from WT mice. Mesenteric arteries from BK \u03b21-KO mice had blunted BK\/enhanced L-type Ca<jats:sup>2+<\/jats:sup>channel function. We conclude that vascular BK channel deficiency exaggerates mortality in septic BK \u03b21-KO mice by activating L-type Ca<jats:sup>2+<\/jats:sup>channels leading to blood pressure-independent tissue ischemia.<\/jats:p>","DOI":"10.1152\/ajpregu.00117.2014","type":"journal-article","created":{"date-parts":[[2014,5,15]],"date-time":"2014-05-15T08:55:42Z","timestamp":1400144142000},"page":"R138-R148","source":"Crossref","is-referenced-by-count":8,"title":["Altered L-type Ca<sup>2+<\/sup>channel activity contributes to exacerbated hypoperfusion and mortality in smooth muscle cell BK channel-deficient septic mice"],"prefix":"10.1152","volume":"307","author":[{"given":"Hui","family":"Xu","sequence":"first","affiliation":[{"name":"Department of Pharmacology and Toxicology,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah","family":"Garver","sequence":"additional","affiliation":[{"name":"Department of Pharmacology and 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