Gap junction currents in cultured muscle cells from human myometrium.

OBJECTIVE: The electrophysiologic properties of gap junctions between human myometrial smooth muscle cells were studied. STUDY DESIGN: Double whole-cell patch clamp recordings were made on pairs of cells from primary cultures of myometrial cells from women undergoing cesarean section. Macroscopic gap junction currents were measured as the change in current in a cell held at a constant voltage while the other member of a pair was subjected to a test pulse of voltage. The blockade by halothane was examined. RESULTS: Mean junctional conductance between pairs of cells was 23 +/- 14 nanosiemens (n = 57). Instantaneous gap junction conductance was constant as a function of transjunctional voltage. For transjunctional voltages of < or = 50 mV, currents were constant during a 5-second test pulse. For larger voltages, however, the currents showed a time-dependent decay. The currents were blocked completely and reversibly with 3.5 mmol/L halothane. Single-channel conductances of 60 picosiemens and 15 picosiemens were observed. CONCLUSION: This first study of gap junction currents in human myometrial cells confirms that connexin43 is the major functional constituent. Functional studies of myometrial gap junction channels may suggest new strategies for controlling uterine contractility.

Voltage-clamp studies of gap junctions between uterine muscle cells during term and preterm labor.

Gap junctions between myometrial cells increase dramatically during the final stages of pregnancy. To study the functional consequences, we have applied the double-whole-cell voltage-clamp technique to freshly isolated pairs of cells from rat circular and longitudinal myometrium. Junctional conductance was greater between circular muscle-cell pairs from rats delivering either at term (32 +/- 16 nS, mean +/- SD, n = 128) or preterm (26 +/- 17 nS, n = 33) compared with normal preterm (4.7 +/- 7.6 nS, n = 114) and postpartum (6.5 +/- 10 nS, n = 16); cell pairs from the longitudinal layer showed similar differences. The macroscopic gap junction currents decayed slowly from an instantaneous, constant-conductance level to a steady-state level described by quasisymmetrical Boltzmann functions of transjunctional voltage. In half of circular-layer cell pairs, the voltage dependence of myometrial gap junction conductance is more apparent at smaller transjunctional voltages (< 30 mV) than for other tissues expressing mainly connexin-43. This unusual degree of voltage dependence, although slow, operates over time intervals that are physiologically relevant for uterine muscle. Using weakly coupled pairs, we observed two unitary conductance states: 85 pS (85-90% of events) and 25 pS. These measurements of junctional conductance support the hypothesis that heightened electrical coupling between the smooth muscle cells of the uterine wall emerges late in pregnancy, in preparation for the massive, coordinate contractions of labor.