Tocolytic desensitization: sodium calcium exchanger function and expression in myometrial relaxation

Preterm birth accounts for $7.4 billion (2002) hospital charges for premature infants. In a paradigm shift to understand tocolytic desensitization, I shifted focus to myometrial relaxation, i.e., decrease in [Ca2+]cyt. Methods: Human myometrial myocytes were obtained from women undergoing cesarean delivery. [Ca2+]cyt was measured using ratiometric imaging. Western blots were stained for NCX1 and smooth muscle actin. Results: Inhibition of NCX increased the rate and amplitude of oxytocin induced oscillations. Terbutaline or Mg2+ blocked oxytocin induced oscillations for 48 hours. After 72 hours, the inhibitory effects of terbutaline and Mg2+ diminished: in vitro desensitized to tocolysis. At 96 hours exposure, full tocolytic desensitization was observed. NCX expression initially increased with tocolytic application (Terbutaline and Mg2+). After 72 hours, the physiological beginning of tocolytic desensitization, NCX protein expression began to decrease. NCX protein expression temporally correlated with tocolytic desensitization. Discussion: This is a novel observation that NCX is a unifying factor in human tocolytic desensitization. Support: Hopkins Women’s Board