Fast voltage-dependent sodium (NaV) currents are functionally expressed in mouse corpus cavernosum smooth muscle cells

Background and Purpose Corpus cavernosum smooth muscle (CCSM) exhibits phasic contractions that are coordinated by ion channels. Mouse models are commonly used to study erectile dysfunction, but there are few published electrophysiological studies of mouse CCSM. We describe the voltage-dependent sodium (Na-V) currents in mouse CCSM and investigate their function. Experimental Approach We used electrophysiological, pharmacological and immunocytochemical methods to study the Na-V currents in isolated CCSM cells from C57BL/6 mice. Tension measurements were carried out using crural sections of the corpus cavernosum in whole tissue. Key Results Fast, voltage-dependent, sodium currents in mouse CCSM were induced by depolarising steps. Steady-state activation and inactivation curves revealed a window current between -60 and -30 mV. Two populations of Na-V currents, 'TTX-sensitive' and 'TTX-insensitive', were identified. TTX-sensitive currents showed 48% block with the Na-V channel subtype-specific blockers ICA-121431 (Na(V)1.1-1.3), PF-05089771 (Na(V)1.7) and 4,9-anhydro-TTX (Na(V)1.6). TTX-insensitive currents were resistant to blockade by A803467, specific for Na(V)1.8 channels. Immunocytochemistry confirmed expression of Na(V)1.5 and Na(V)1.4 in freshly dispersed CCSM cells. Veratridine, a Na-V channel activator, reduced time-dependent inactivation of Na-V currents and increased duration of evoked action potentials. Veratridine induced phasic contractions in CCSM strips, reversible with TTX and nifedipine but not KB-R7943. Conclusion and Implications There are fast, voltage-dependent, sodium currents in mouse CCSM. Stimulation of these currents increased contractility of CCSM in vitro, suggesting an involvement in detumescence and potentially providing a clinically relevant target in erectile dysfunction. Further work will be necessary to define its role.