Voltage-clamp analysis of transmembrane ionic currents in guinea-pig myometrium: evidence for an initial potassium activation triggered by calcium influx

Abstract

Voltage-clamp analysis of ionic transmembrane currents in very small strands of guinea-pig myometrium was carried out with a double sucrose-gap technique. It was found that the electrical activity, consisting of a spike followed by a long plateau, is controlled by, at least, four ionic conductances. (1) A fast inward current is responsible for the spike generation. Its low equilibrium potential accounts, partly, for the low amplitude of the spike. (2) The fast inward current is antagonized by an early outward current which occurs almost simultaneously. This fast outward current is blocked by TEA. Its reversal potential is about -95 mV. A tenfold increase in the external K-concentration shifts the reversal potential by 50 mV. Thus, it is concluded that the initial outward current is carried by K+. (3) A slow current, whose reversal potential ranges from -40 to -10 mV, is responsible for the negative after-potential. Cl-depletion (to one-ninth) does not modify this current while Na-depletion (to one-ninth) decreases its reversal potential by about 20 mV. (4) A late current which shows delayed rectification is elicited by long pulses. Its analysis is made difficult by the change mainly of the K-equilibrium potential suggesting accumulation of K+ outside the cell membrane. (5) The availability of the inward current and of the slow current, determined in TEA solution, shows that both currents are half-inactivated by a 8 mV conditioning depolarization. Using a slope factor of -2-5 or -3 the availability curve fits the experimental values. In normal solution, the availability curve of the initial current appears complex in the hyperpolarization range. The fast outward current, which is partly inactivated at the resting potential, is restored by conditioning hyperpolarization and then antagonizes the Ca inward current more. (6) It is concluded that the fast K-current controls the spike generation and accounts for the fast repolarization of the spike. The fast and transient increase in K-conductance may be the result of a momentary local increase in Ca concentration at the internal surface of the membrane.