Fast voltage-dependent sodium (Na_V ) 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.