Nongenomic actions of progesterone and 17β-estradiol on the chloride conductance of skeletal muscle

Introduction: Myotonia congenita, caused by mutations in ClC-1, tends to be more severe in men and is often exacerbated by pregnancy. Methods: We performed whole-cell patch clamp of mouse muscle chloride currents in the absence/presence of 100 μM progesterone or 17β-estradiol. Results: 100 μM progesterone rapidly and reversibly shifted the ClC-1 activation curve of mouse skeletal muscle (V50 changed from −52.6 ± 9.3 to +35.5 ± 6.7; P < 0.01) and markedly reduced chloride currents at depolarized potentials. 17β-estradiol at the same concentration had a similar but smaller effect (V50 change from −57.2 ± 7.6 to −40.5 ± 9.8; P < 0.05). 1 μM progesterone produced no significant effect. Conclusions: Although the data support the existence of a nongenomic mechanism in mammalian skeletal muscle through which sex hormones at high concentration can rapidly modulate ClC-1, the influence of hormones on muscle excitability in vivo remains an open question. Muscle Nerve 48: 589–591, 2013