The effects of pH change on Ca⁺⁺ signaling and force in pregnant human myometrium

OBJECTIVE: This study was designed to determine the effects of both intracellular and extracellular pH change on contractile activity and intracellular Ca⁺⁺ during spontaneous contractions, oxytocin, and depolarization-induced stimulation of human myometrium. STUDY DESIGN: Human myometrial tissue was obtained at elective caesarean delivery at term (37-41 completed weeks of gestation). Longitudinal strips were dissected and loaded with the calcium sensitive indicator Indo-1. Statistical significance was tested with the Student t test. RESULTS: Both intracellular and extracellular acidification significantly reduces or even abolishes phasic activity, whether it arises spontaneously or in the presence of oxytocin. These contractile changes can be accounted for by the changes in intracellular Ca⁺⁺. Alkalinization produced the opposite effects. However, baseline or maintained tension changes could not be accounted for by changes in intracellular Ca⁺⁺. CONCLUSION: We suggest that the effects on phasic activity are due to the inhibition of L-type calcium entry and that, during maintained or baseline activity, pH-sensitive Ca⁺⁺ release, possibly from the sarcoplasmic reticulum occurs; but it is insufficient to overcome the inhibitory effects at the myofilaments. We conclude that alterations of pH significantly affect calcium signaling and force production in the human myometrium and may contribute to dysfunction in labor.