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 t hat increases intracellular free calcium ([Ca++](i)) in several tissue s. Calcium homeostasis is central to the excitation and relaxation of uterine muscle during labor. The present study, therefore, investigate d whether lindane exposure modulated [Ca++](i) in myometrial smooth mu scle cells. This study demonstrated that lindane, but not beta-hexachl orocyclohexane, increased [Ca++](i) in a concentration-dependent manne r in individual rat myometrial cells, as measured with the calcium-sen sitive probe fura-P-AM. The lindane-induced Ca++ response was rapid in onset end protracted in duration. The lindane response was apparently independent of external calcium because equivalent [Ca++](i) response s were observed in cells exposed to lindane in Ca++-containing and Ca+-free media and in the presence of 10 mu M nifedipine, a dihydropyrid ine blocker of plasma membrane voltage-sensitive Ca++ channels. Prior depletion of internal Ca++ stores that contained Ca++-induced Ca++-rel ease channels by 10 mM caffeine and 1 mu M ryanodine did not affect li ndane's ability to increase [Ca++](i), whereas pretreatment with eithe r 1 mu M ionomycin or 5 mu M 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 co ncentrations of lindane (1 mu M) rapidly inhibited the regenerative ca lcium oscillations induced by carbachol. If the mechanism is similar i n vivo, lindane exposure may perturb many finely regulated Ca++-depend ent processes required for excitation-contraction coupling in successf ul parturition and, therefore, increase the probability of delayed or dysfunctional labor.