Abstract

The effects of organophosphate (OP) paraoxon, active metabolite of parathion, were studied on the Ca2+ and Ba2+ spikes and on the excitability of the neuronal soma membranes of land snail (Caucasotachea atrolabiata). Paraoxon (0.3 mu M) reversibly decreased the duration and amplitude of Ca2+ and Ba2+ spikes. It also reduced the duration and the amplitude of the afterhyperpolarization (AHP) that follows spikes, leading to a significant increase in the frequency of Ca2+ spikes. Pretreatment with atropine and hexamethonium, selective blockers of muscarinic and nicotinic receptors, respectively, did not prevent the effects of paraoxon on Ca2+ spikes. Intracellular injection of the calcium chelator BAPTA dramatically decreased the duration and amplitude of AHP and increased the duration and frequency of Ca2+, spikes. In the presence of BAPTA, paraoxon decreased the duration of the Ca2+ spikes without affecting their frequency. Apamin, a neurotoxin from bee venom, known to selectively block small conductance of calcium-activated potassium channels (SK), significantly decreased the duration and amplitude of the AHP, an effect that was associated with an increase in spike frequency. in the presence of apamin, bath application of paraoxon reduced the duration of Ca2+ spike and AHP and increased the firing frequency of nerve cells. in summary, these data suggest that exposure to submicromolar concentration of paraoxon may directly affect membrane excitability. Suppression of Ca2+ entry during the action potential would down regulate Ca2+-activated K+ channels leading to a reduction of the AHP and an increase in cell firing. (c) 2006 Elsevier B.V. All rights reserved.