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Articles in PresS, published online ahead of print September 27, 2002
J Appl Physiol, 10.1152/jap.00660.2002
Submitted on July 18, 2002
Accepted on September 7, 2002
1 Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada
2 Lawson Health Research Institute, St. Joseph's Health Centre, London, Ontario, Canada
3 Department of Surgery, The University of Western Ontario, London, Ontario, Canada; Lawson Health Research Institute, St. Joseph's Health Centre, London, Ontario, Canada
* To whom correspondence should be addressed. E-mail: Stephen.Sims{at}fmd.uwo.ca.
Little is known of the excitatory mechanisms that contribute to the tonic contraction of the corpus cavernosum smooth muscle in the flaccid state. We used patch-clamp electrophysiology to investigate a previously unidentified inward current in freshly isolated rat and human corporal myocytes. Phenylephrine (PE) contracted cells and activated whole-cell currents. Outward current was identified as large-conductance Ca2+ -activated K+ current. The inward current elicited by PE was dependent on the Cl- gradient and inhibited by niflumic acid, indicative of a Ca2+ -activated Cl- (ClCa) current. Furthermore, spontaneous transient outward and inward currents (STOCs and STICs) were identified in both rat and human corporal myocytes, and derived from BKCa and ClCa channel activity. STICs and STOCs were inhibited by PE and A-23187, and combined 8-br-cAMP and 8-br-cGMP decreased their frequency. When studied in vivo, chloride channel blockers transiently increased intracavernosal pressure and prolonged nerve-evoked erections. This report reveals for the first time ClCa current in rat and human corpus cavernosum SMCs, and demonstrates its key functional role in the regulation of penile erection.
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