Ca2+-activated Cl− channels in corpus cavernosum smooth muscle: a novel mechanism for control of penile erection

Author:

Karkanis Tom1,DeYoung Ling2,Brock Gerald B.32,Sims Stephen M.1

Affiliation:

1. Departments of Physiology and Pharmacology and

2. Lawson Health Research Institute, St. Joseph's Health Centre, London, Ontario, Canada N6A 5C1

3. Surgery, The University of Western Ontario, London, Ontario, and

Abstract

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 was inhibited by niflumic acid, indicative of a Ca2+-activated Cl (ClCa) 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 Ca2+-activated K+ and ClCa 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 ClCa current in rat and human corpus cavernosum smooth muscle cells and demonstrates its key functional role in the regulation of penile erection.

Publisher

American Physiological Society

Subject

Physiology (medical),Physiology

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