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From the Department of Pharmacology, State University of New York Health Science Center, Brooklyn, New York 11203

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 of 0.2 ms at 20 mV, and inactivates as a single exponential with a of 0.4 ms. Na⁺ conductance is half activated at –21.5 mV, and half inactivated at –59 mV. I_Na reactivates with a of 20 ms. I_Ca is abolished by Ca²⁺-free medium, Co²⁺ (5 mM), or nisoldipine (2 µM), and enhanced in 30 mM Ca²⁺, Ba²⁺, or BAY-K 8644. It first appears at –30 mV and reaches maximum at +10 mV. It activates with a voltage-dependent of 1.5 ms at 20 mV, and inactivates in two exponential phases, with 's of 33 and 133 ms. Ca²⁺ conductance is half activated at –7.4 mV, and half inactivated at –34 mV. I_Ca reactivates with '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.

Key Words: smooth muscle cells • Na⁺ channels • Ca²⁺ channels • estrogen • pregnancy

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