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

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 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.

Methylmercury Induces a Spontaneous, Transient Slow Inward Chloride Current in Purkinje Cells of Rat Cerebellar Slices

“…Spontaneous transient depolarizing potentials or inward currents in smooth muscle or interstitial cells are the result of release of Ca 2ϩ from intracellular stores and subsequent activation of Ca 2ϩ -activated Cl Ϫ channels (Sergeant et al, 2001;Karkanis et al, 2003;Craven et al, 2004). Elevation of [Ca 2ϩ ] i is seen with MeHg in many types of neurons, including cerebellar granule and Purkinje cells (Marty and Atchison, 1997;Limke et al, 2003;Edwards et al, 2005).…”

Regulation of intracellular Ca2+ release in corpus cavernosum smooth muscle: synergism between nitric oxide and cGMP

“…No differences in the responses to phenylephrine (PE) or S-nitroso-N-acetylpenicillamine (SNAP) and sildenafil were observed among the cells from different sources. Segments of cavernosal tissue (ϳ1 mm 2 ) were dissociated as described previously (20). Measurement of [Ca 2ϩ ]i.…”

T-type Ca2+ channels in non-vascular smooth muscles

“…K + channels that may relax corpus cavernosum have been recorded, in part motivated to understand more about the aetiology of erectile dysfunction and the only depolarising current studied is a Ca 2+ -activated Cl -current [62]. Vas deferens smooth muscle has received most attention and in human myocytes an L-type and Ttype current have been recorded, with the T-type current contributing about 20% of the total inward current [63].…”