Effects of Sodium and Calcium Channel Blockade on Cytosolic Calcium Oscillations and Phasic Contractions of Myometrial Tissue

Abstract

Objective: These studies sought to test the hypothess that agonist-stimulated cytosolic calcium oscillations and phasic myometrial contractions are dependent on calcium influx through dihydropyridine-sensitive calcium channels, but not sodium influx through tetrodotoxin-sensitive sodium channels.

Methods: Cytosolic calcium imaging studies and in vitro isometric contraction studies were performed using uterine tissue from proestrus/estrus Sprague-Dawley rats. The calcium imaging studies were performed after loading parital thickness strips of myometrium with Fura-2. For the in vitro isometric contraction studies, the contraction data were computer digitalized, analyzed for contraction area, and normalized for cross-section area. The effects of nifedipine (1.0-5 μmol/L), a calcium channel blocker, were compared to tetrodotoxin (0.01-1 μmol/L), a sodium channel blocker.

Results: Oxytocin-stimulted simultaneous cytosolic calcium oscillations and phasic contractions were completely inhibited by 1 μmol/L nifedipine; in contrast, 1 μmol/L tetrodotoxin had no effect on the oxytocin-stimulated oscillations and contractions. Oxytocin, aluminum fluoride, potassium chloride, and ionomycin stimulated in vitro phasic myometrial contractions. Tetrodotoxin had no effect on these agonist-stimulated phasic contractions, whereas nifedipine produced a significant, dose-related inhibition of the phasic contractile activity.

Conclusions: The studies described in this report support the hypothesis that the influx of extracellular calcium is an important component of the cellular mechanisms responsible for the cytosolic calcium oscillations occurring during phasic myometrial contractions. In contrast, sodium influx through tetrodotoxinsensitive sodium channels does not appear to play a comparably important role.

Keywords

Calcium channel oxytocin phasic myometrial contractions nifedipine sodium channel tetrodotoxin

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