Lindane increases intracellular calcium in rat myometrial smooth muscle cells through modulation of inositol 1,4,5-trisphosphate-sensitive stores.

Lindane (gamma-hexachlorocyclohexane) is an organochlorine pesticide that increases intracellular free calcium ([Ca++]i) in several tissues. Calcium homeostasis is central to the excitation and relaxation of uterine muscle during labor. The present study, therefore, investigated whether lindane exposure modulated [Ca++]i in myometrial smooth muscle cells. This study demonstrated that lindane, but not beta-hexachlorocyclohexane, increased [Ca++]i in a concentration-dependent manner in individual rat myometrial cells, as measured with the calcium-sensitive probe fura-2-AM. The lindane-induced Ca++ response was rapid in onset and protracted in duration. The lindane response was apparently independent of external calcium because equivalent [Ca++]i responses were observed in cells exposed to lindane in Ca(++)-containing and Ca(++)-free media and in the presence of 10 microM nifedipine, a dihydropyridine blocker of plasma membrane voltage-sensitive Ca++ channels. Prior depletion of internal Ca++ stores that contained Ca(++)-induced Ca(++)-release channels by 10 mM caffeine and 1 microM ryanodine did not affect lindane's ability to increase [Ca++]i, whereas pretreatment with either 1 microM ionomycin or 5 microM carbachol eliminated the lindane-induced [Ca++]i increase. These experiments suggest that lindane increases [Ca++]i through the selective release of inositol 1,4,5-trisphosphate-sensitive Ca++ stores. In addition, in Ca(++)-containing buffer, low concentrations of lindane (1 microM) rapidly inhibited the regenerative calcium oscillations induced by carbachol. If the mechanism is similar in vivo, lindane exposure may perturb many finely regulated Ca(++)-dependent processes required for excitation-contraction coupling in successful parturition and, therefore, increase the probability of delayed or dysfunctional labor.