EFFECTS OF SODIUM AND CALCIUM-CHANNEL BLOCKADE ON CYTOSOLIC CALCIUM OSCILLATIONS AND PHASIC CONTRACTIONS OF MYOMETRIAL TISSUE

OBJECTIVE: The studies sought to test the hypothesis that agonist-stim ulated cytosolic calcium oscillations and phasic myometrial contractio ns are dependent on calcium influx through dihydropyridine-sensitive c alcium channels, but not sodium influx through tetrodotoxin-sensitive sodium channels. METHODS: Cytosolic calcium imaging studies and in vit ro isometric contraction studies were performed using uterine tissue f rom proestrus/estrus Sprague-Dawley rats. The calcium imaging studies were performed after loading partial thickness strips of myometrium wi th Fura-2. For the in vitro isometric contraction studies, the contrac tion data were computer digitalized, analyzed for contraction area, an d normalized for cross-section area. The effects of nifedipine (1.0-5 mu mol/L), a calcium channel blocker, were compared to tetrodotoxin (0 .01-1 mu mol/L), a sodium channel blocker. RESULTS: Oxytocin-stimulate d simultaneous cytosolic calcium oscillations and phasic contractions were completely inhibited by 1 mu mol/L nifedipine; in contrast, 1 mu mol/L tetrodotoxin had no effect on the oxytocin-stimulated calcium os cillations and contractions. Oxytocin, aluminum fluoride, potassium ch loride, and ionomycin stimulated in vitro phasic myometrial contractio n. Tetrodotoxin had no effect on these agonist-stimulated phasic contr actions, whereas nifedipine produced a significant, dose-related inhib ition of the phasic contractile activity. CONCLUSIONS: The studies des cribed in this report support the hypothesis that the influx of extrac ellular calcium is an important component of the cellular mechanisms r esponsible for the cytosolic calcium oscillations occurring during pha sic myometrial contraction. In contrast, sodium influx through tetrodo toxin-sensitive sodium channels does not appear to play a comparably i mportant role. Copyright (C) 1997 by the Society for Gynecologic Inves tigation.