Lindane (gamma-Hexachlorocyclohexane) Induces Internal Ca2+ Release and Capacitative Ca2+ Entry in Madin-Darby Canine Kidney Cells

Abstract

The effect of lindane (gamma-hexachlorocyclohexane), an organochlorine pesticide, on Ca2+ mobilization in Madin-Darby canine kidney cells was examined by fluorimetry using fura-2 as a Ca2+ indicator. Lindane (5-200 microM) increased [Ca2+]i concentration-dependently. The [Ca2+]i signal comprised an immediate initial rise followed by a persistent phase. Ca2+ removal inhibited the [Ca2+]i signal by reducing both the initial rise and the sustained phase. This implies lindane-triggered Ca2+ influx and Ca2+ release. In Ca2+ -free medium, 0.15 mM lindane increased [Ca2+]i after pretreatment with carbonylcyanide m-chlorophenylhydrazone (CCCP, 2 microM), a mitochondrial uncoupler, and two endoplasmic reticulum Ca2+ pump inhibitors, thapsigargin and cyclopiazonic acid. Conversely, pretreatment with lindane abolished CCCP- and thapsigargin-induced Ca2+ release. This suggests that 0.15 mM lindane released Ca2+ from the endoplasmic reticulum, mitochondria and other stores. La3+ (1 mM) partly inhibited 0.1 mM lindane-induced [Ca2+]i increase, confirming that lindane induced Ca2+ influx. Addition of 3 mM Ca2+ increased [Ca2+]i after pretreatment with 0.15 mM lindane for 750 sec. in Ca2+ -free medium, which indicates lindane-induced capacitative Ca2+ entry. Lindane (0.15 mM)-induced Ca2+ release was not reduced by inhibiting phospholipase C with 2 microM U73122, but was inhibited by 70% by the phospholipase A2 inhibitor aristolochic acid (40 microM).

Cardiotoxicité du lindane, un isomère γ de l’hexachlorocyclohexane

“…1 ). Une libération de Ca 2+ à partir du RE, des mitochondries et autres réservoirs calciques a été observée en présence de lindane (0,15 m M) dans les cellules rénales de Chat (Lu et al, 2000); cette libération de Ca 2+ n'était pas altéré par l'inhibiteur de la phospholipase C (U73122, 2 µM) mais était inhibé de 70 % par l'acide aristocholique (40 µM), un inhibiteur de la phospholipase A2. Le lindane altère le métabolisme énergétique des mitochondries hépatiques (Srinivasan & Radhakrishnamurty, 1988); il diminue la prise de glucose et la synthèse de l'inositol-phosphate des cellules neuronals (Pulido et al, 1992).…”

Does lindane (gamma-hexachlorocyclohexane) increase the rapid delayed rectifier outward K+ current (I Kr) in frog atrial myocytes?

“…Lindane (1 microM – 100 microM) does not depress the peak of intracellular Ca 2+ transient in guinea pig myocytes, and does not interact directly with the ryanodine receptor Ca 2+ release channels from cardiac sarcoplasmic reticulum vesicles [9]. A Ca 2+ release from the endoplasmic reticulum, mitochondria and other Ca 2+ stores has been reported in the presence of lindane (0.15 mM) in cat kidney cells [10]. Lindane (30 microM) has no effect on the L-type Ca 2+ current, but suppresses the activity of large conductance Ca 2+ -activated K + channels and increases the firing rate of spontaneous action potentials in rat pituitary GH(3) cells [11].…”

Phosphoinositide and phospholipid phosphorylation and hydrolysis pathways<br/>—Organophosphate and organochlorine pesticides effects<br>

“…Lu et al [41] from the endoplasmic reticulum, mitochondria and other stores. However, Lindane (0.15 mM)-induced Ca 2+ release was not reduced by inhibiting PLC with 2 μM U73122, thus also indicating that a mechanism similar to the activation of PLC, but different from this one, as the responsible for the OC effect.…”