Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons: Relevance to the hyperexcitability induction.
The effects of organophosphate (OP) paraoxon, active metabolite of parathion, were studied on the Ca(2+) and Ba(2+) spikes and on the excitability of the neuronal soma membranes of land snail (Caucasotachea atrolabiata). Paraoxon (0.3 muM) reversibly decreased the duration and amplitude of Ca(2+) and Ba(2+) 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 Ca(2+) spikes. Pretreatment with atropine and hexamethonium, selective blockers of muscarinic and nicotinic receptors, respectively, did not prevent the effects of paraoxon on Ca(2+) spikes. Intracellular injection of the calcium chelator BAPTA dramatically decreased the duration and amplitude of AHP and increased the duration and frequency of Ca(2+) spikes. In the presence of BAPTA, paraoxon decreased the duration of the Ca(2+) 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 Ca(2+) 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 Ca(2+) entry during the action potential would down regulate Ca(2+)-activated K(+) channels leading to a reduction of the AHP and an increase in cell firing.
Department of Physiology and Neuroscience Research Center, Faculty of Medicine, Shaheed Beheshti Medical Sciences University, PO Box 19835-181, Evin, Tehran, Iran.
Jafar
J
Vatanparast
Mahyar
M
Janahmadi
Ali Reza
AR
Asgari
Houri
H
Sepehri
Ali
A
Haeri-Rohani
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D001030:Apamin / Q000494:pharmacology; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects* / Q000502:physiology; D002490:Central Nervous System / Q000187:drug effects* / Q000378:metabolism; D002614:Chelating Agents / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D017952:Ganglia, Invertebrate / Q000187:drug effects* / Q000378:metabolism; D018727:Muscarinic Antagonists / Q000494:pharmacology; D009474:Neurons / Q000187:drug effects* / Q000378:metabolism; D018733:Nicotinic Antagonists / Q000494:pharmacology; D010261:Paraoxon / Q000494:pharmacology*; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000037:antagonists & inhibitors / Q000378:metabolism; D011950:Receptors, Cholinergic / Q000187:drug effects / Q000378:metabolism; D012908:Snails / Q000187:drug effects* / Q000378:metabolism
D002614:Chelating Agents; D002800:Cholinesterase Inhibitors; D018727:Muscarinic Antagonists; D018733:Nicotinic Antagonists; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D011950:Receptors, Cholinergic; D001030:Apamin; D010261:Paraoxon; D002118:Calcium