PARTITION OF THE ORGANOCHLORINE INSECTICIDE LINDANE INTO THE HUMAN SPERM SURFACE INDUCES MEMBRANE DEPOLARIZATION AND CA2+ INFLUX

The effects of the insecticide lindane (the gamma-isomer of 1,2,3,4,5, 6-hexachlorocyclohexane) on membrane potential, cytosolic free Ca2+ co ncentration ([Ca2+](i)) and surface biophysical properties were studie d in human spermatozoa. The insecticide induces rapid, transient and r eproducible membrane depolarization and opening of voltage-dependent C a2+ channels leading to an increase in [Ca2+](i). In contrast with the effect in somatic cells, lindane did not affect gamma-aminobutyric ac id receptor-linked Cl- currents. Ca2+ and K+ currents were found to dr ive lindane-induced membrane depolarization and repolarization respect ively, whereas Na+ and Cl- fluxes appear not to have a role in the phe nomenon. The insecticide was still able to produce membrane depolariza tion both in the combined absence of extracellular Ca2+ and Na+ and in high-K+ buffer, suggesting that lindane alters the membrane dipole po tential. In agreement with this, Laurodan and Prodan fluorescence spec troscopy revealed that lindane partition into the sperm plasma membran e lowers water molecular dynamics in the uppermost region of the membr ane external leaflet, probably as the result of reordering of water di poles. We propose that the first effect of lindane partitioning into t he sperm plasma membrane is a change in the membrane dipole potential, which results in the activation of membrane-located Ca2+-influx pathw ays.