Molecular and functional characterisation of Kv7 channels in the penis of healthy and metabolic syndrome rats

KCNQ-encoded voltage-dependent potassium channels (Kv7) are involved in regulation of vascular tone. This study evaluated the influence of Kv7 channel-activation on smooth muscle relaxation in rat penile arteries (PA) and corpus cavernosum (CC) from normal and Spontaneous Hypertensive prone to Heart Failure (SHHF) rats - a rat model of human metabolic syndrome.

qPCR and immunohistochemistry was used to determine the expression of KCNQ isoforms in penile tissue. Isometric tension was measured in intracavernous arterial rings and corpus cavernosum strips isolated from normal and SHHF rats.

KCNQ3, KCNQ4, and KCNQ5 were detected in PA and CC (n=5). KCNQ1 was only found in CC (n=5). Immunofluorescence signals to Kv7.4 and Kv7.5 were found in PA, penile vein and the trabeculae of CC. Kv7.1 was detected in the CC and corpus spongiosum (n=5). The Kv7.2-7.5 activators, N-mesitylbicyclo[2.2.1]heptane-2-carboxamide (ML213) and (3S)-(+)-(5-chloro-2-methoxyphenyl)-1,3-dihydro-3-fluoro-6-(trifluoromethyl)-2H-indol-2-one (BMS204352), relaxed precontracted PA and CC (n=5). Relaxations to sildenafil and an NO donor were reduced by blocking Kv7 channels with linopirdine in PA and CC (n=5-6, Two-way ANOVA, p<0.05). In SHHF rat PA and CC, relaxations to ML213 and BMS204352, were attenuated, and the blocking effect of linopirdine on sildenafil- and SNP-induced relaxations reduced (n=5-6, Two-way ANOVA, p<0.05). KCNQ3, KCNQ4, and KCNQ5 were downregulated and KCNQ1 was upregulated in CC from SHHF rats (n=5-8, Mann Whitney, p<0.05). KCNQ1-5 transcripts remained unchanged in PA from SHHF rats (n=5, Mann Whitney, p<0.05).

These data suggest that Kv7 channels play a role in erectile function and contribute to the pathophysiology of erectile dysfunction, an early indicator of cardiovascular disease.