{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,11,3]],"date-time":"2025-11-03T08:16:03Z","timestamp":1762157763132,"version":"3.41.0"},"reference-count":39,"publisher":"American Physiological Society","issue":"5","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["American Journal of Physiology-Cell Physiology"],"published-print":{"date-parts":[[2017,11,1]]},"abstract":"<jats:p>Rabbit corpus cavernosum smooth muscle (RCCSM) cells express ion channels that produce Ca<jats:sup>2+<\/jats:sup>-activated Cl<jats:sup>\u2212<\/jats:sup>( I<jats:sub>ClCa<\/jats:sub>) current, but low sensitivity to conventional antagonists has made its role in tone generation difficult to evaluate. We have reexamined this question using two new generation I<jats:sub>ClCa<\/jats:sub>blockers, T16A<jats:sub>inh<\/jats:sub>-A01 and CaCC<jats:sub>inh<\/jats:sub>-A01. Isolated RCCSM cells were studied using the perforated patch method. Current-voltage protocols revealed that both L-type Ca<jats:sup>2+<\/jats:sup>current and I<jats:sub>ClCa<\/jats:sub>. T16A<jats:sub>inh<\/jats:sub>-A01 and CaCC<jats:sub>inh<\/jats:sub>-A01 (10 \u03bcM) reduced I<jats:sub>ClCa<\/jats:sub>by ~85%, while 30 \u03bcM abolished it. L-type Ca<jats:sup>2+<\/jats:sup>current was unaffected by 10 \u03bcM CaCC<jats:sub>inh<\/jats:sub>-A01 but was reduced by 50% at 30 \u03bcM CaCC<jats:sub>inh<\/jats:sub>-A01, 46% at 10 \u03bcM T16A<jats:sub>inh<\/jats:sub>-A01, and 78% at 30 \u03bcM T16A<jats:sub>inh<\/jats:sub>-A01. Both drugs reduced spontaneous isometric tension in RCCSM strips, by 60\u201370% at 10 \u03bcM and &gt;90% at 30 \u03bcM. Phenylephrine (PE)-enhanced tension was also reduced (ED<jats:sub>50<\/jats:sub>\u2009=\u20093 \u03bcM, CaCC<jats:sub>inh<\/jats:sub>-A01; 14 \u03bcM, T16A<jats:sub>inh<\/jats:sub>-A01). CaCC<jats:sub>inh<\/jats:sub>-A01 at 10 \u03bcM had little effect on 60 mM KCl contractures, though they were reduced by 30 \u03bcM CaCC<jats:sub>inh<\/jats:sub>-A01 and T16A<jats:sub>inh<\/jats:sub>-A01 (10 \u03bcM and 30 \u03bcM) consistent with their effects on L-type Ca<jats:sup>2+<\/jats:sup>current. Both drugs also reversed the stimulatory effect of PE on intracellular Ca<jats:sup>2+<\/jats:sup>waves, studied with laser scanning confocal microscopy in isolated RCCSM cells. In conclusion, although both drugs were effective blockers of I<jats:sub>ClCa<\/jats:sub>, the effect of T16A<jats:sub>inh<\/jats:sub>-A01 on L-type Ca<jats:sup>2+<\/jats:sup>current precludes its use for evaluating the role of I<jats:sub>ClCa<\/jats:sub>in tone generation. However, 10 \u03bcM CaCC<jats:sub>inh<\/jats:sub>-A01 selectively blocked I<jats:sub>ClCa<\/jats:sub>versus L-type Ca<jats:sup>2+<\/jats:sup>current and reduced spontaneous and PE-induced tone, suggesting that I<jats:sub>ClCa<\/jats:sub>is important in maintaining penile detumescence.<\/jats:p>","DOI":"10.1152\/ajpcell.00025.2017","type":"journal-article","created":{"date-parts":[[2017,8,24]],"date-time":"2017-08-24T01:11:49Z","timestamp":1503537109000},"page":"C475-C486","source":"Crossref","is-referenced-by-count":11,"title":["The role of Ca<sup>2+<\/sup>-activated Cl<sup>\u2212<\/sup>current in tone generation in the rabbit corpus cavernosum"],"prefix":"10.1152","volume":"313","author":[{"given":"Karen I.","family":"Hannigan","sequence":"first","affiliation":[{"name":"Smooth Muscle Research Centre, Dundalk Institute of Technology, Dundalk, Ireland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Caoimhin 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