Ca2+-activated Cl- channels in corpus cavernosum smooth muscle: a novel mechanism for control of penile erection.
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 Ca(2+)-activated K(+) current. The inward current elicited by PE was dependent on the Cl(-) gradient and was inhibited by niflumic acid, indicative of a Ca(2+)-activated Cl(-) (Cl(Ca)) current. Furthermore, spontaneous transient outward and inward currents (STOCs and STICs, respectively) were identified in both rat and human corporal myocytes and derived from large-conductance Ca(2+)-activated K(+) and Cl(Ca) channel activity. STICs and STOCs were inhibited by PE and A-23187, and combined 8-bromoadenosine cAMP and 8-bromoadenosine 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 Cl(Ca) current in rat and human corpus cavernosum smooth muscle cells and demonstrates its key functional role in the regulation of penile erection.
Karkanis
Tom
T
Department of Physiology and Pharmacology, The University of Western Ontario, London, Ontario, Canada N6A 5C1.
DeYoung
Ling
L
Brock
Gerald B
GB
Sims
Stephen M
SM
D000316:Adrenergic alpha-Agonists / Q000494:pharmacology; D000818:Animals; D002118:Calcium / Q000378:metabolism*; D018118:Chloride Channels / Q000037:antagonists & inhibitors / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D004553:Electric Conductivity; D006801:Humans; D008297:Male; D009119:Muscle Contraction; D009130:Muscle, Smooth / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D032389:Myocytes, Smooth Muscle / Q000502:physiology; D009712:Nucleotides, Cyclic / Q000494:pharmacology; D018408:Patch-Clamp Techniques; D010410:Penile Erection / Q000187:drug effects / Q000502:physiology*; D010413:Penis / Q000166:cytology / Q000187:drug effects / Q000378:metabolism* / Q000502:physiology; D010656:Phenylephrine / Q000494:pharmacology; D011312:Pressure; D051381:Rats; D017207:Rats, Sprague-Dawley
D000316:Adrenergic alpha-Agonists; D018118:Chloride Channels; D009712:Nucleotides, Cyclic; D010656:Phenylephrine; D002118:Calcium