Sodium and Calcium Inward Currents in Freshly Dissociated Smooth Myocytes of Rat Uterus

Freshly dissociated myocytes from nonpregnant, pregnant, and postpartum rat uteri have been studied with the tight-seal patch-clamp method. The inward current contains both I(Na) and I(Ca) that are vastly different from those in tissue-cultured material. I(Na) is abolished by Na(+)-free medium and by 1 μM tetrodotoxin. It first appears at ∼−40 mV, reaches maximum at 0 mV, and reverses at 84 mV. It activates with a voltage-dependent τ of 0.2 ms at 20 mV, and inactivates as a single exponential with a τ of 0.4 ms. Na(+) conductance is half activated at −21.5 mV, and half inactivated at −59 mV. I(Na) reactivates with a τ of 20 ms. I(Ca) is abolished by Ca(2+)-free medium, Co(2+) (5 mM), or nisoldipine (2 μM), and enhanced in 30 mM Ca(2+), Ba(2+), or BAY-K 8644. It first appears at ∼−30 mV and reaches maximum at +10 mV. It activates with a voltage-dependent τ of 1.5 ms at 20 mV, and inactivates in two exponential phases, with τ's of 33 and 133 ms. Ca(2+) conductance is half activated at −7.4 mV, and half inactivated at −34 mV. I(Ca) reactivates with τ's of 27 and 374 ms. I(Na) and I(Ca) are seen in myocytes from nonpregnant estrus uteri and throughout pregnancy, exhibiting complex changes. The ratio of densities of peak I(Na)/I(Ca) changes from 0.5 in the nonpregnant state to 1.6 at term. The enhanced role of I(Na), with faster kinetics, allows more frequent repetitive spike discharges to facilitate simultaneous excitation of the parturient uterus. In postpartum, both currents decrease markedly, with I(Na) vanishing from most myocytes. Estrogen-enhanced genomic influences may account for the emergence of I(Na), and increased densities of I(Na) and I(Ca) as pregnancy progresses. Other influences may regulate varied channel expression at different stages of pregnancy.