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 INa and ICa that are vastly different from those in tissue-cultured material. INa is abolished by Na+-free medium and by 1 microM tetrodotoxin. It first appears at approximately -40 mV, reaches maximum at 0 mV, and reverses at 84 mV. It activates with a voltage-dependent tau of 0.2 ms at 20 mV, and inactivates as a single exponential with a tau of 0. 4 ms. Na+ conductance is half activated at -21.5 mV, and half inactivated at -59 mV. INa reactivates with a tau of 20 ms. ICa is abolished by Ca2+-free medium, Co2+ (5 mM), or nisoldipine (2 microM), and enhanced in 30 mM Ca2+, Ba2+, or BAY-K 8644. It first appears at approximately -30 mV and reaches maximum at +10 mV. It activates with a voltage-dependent tau of 1.5 ms at 20 mV, and inactivates in two exponential phases, with tau's of 33 and 133 ms. Ca2+ conductance is half activated at -7.4 mV, and half inactivated at -34 mV. ICa reactivates with tau's of 27 and 374 ms. INa and ICa are seen in myocytes from nonpregnant estrus uteri and throughout pregnancy, exhibiting complex changes. The ratio of densities of peak INa/ICa changes from 0.5 in the nonpregnant state to 1.6 at term. The enhanced role of INa, with faster kinetics, allows more frequent repetitive spike discharges to facilitate simultaneous excitation of the parturient uterus. In postpartum, both currents decrease markedly, with INa vanishing from most myocytes. Estrogen-enhanced genomic influences may account for the emergence of INa, and increased densities of INa and ICa as pregnancy progresses. Other influences may regulate varied channel expression at different stages of pregnancy.