title: Forskolin potentiates the paraoxon-induced hyperexcitability in snail neurons by blocking afterhyperpolarization.
abstract: One characteristic of organophosphate poisoning is the ability to increase excitability or induce epileptiform activity in nerve cells, but underlying mechanisms are not fully understood. We have previously reported that paraoxon, an organophosphate compound, at submicromolar concentrations effectively suppress Ca(2+) spikes and modulate the activity of snail neurons. This effect was unrelated to acetylcholinesterase (AChE) inhibition but was found to involve the direct or indirect modulation of ion channels [Vatanparast J, Janahmadi M, Asgari AR, Sepehri H, Haeri-Rohani A. Paraoxon suppresses Ca(2+) spike and afterhyperpolarization in snail neurons: relevance to the hyperexcitability induction. Brain Res 2006a;1083(1):110-7]. In the present study, the interaction of paraoxon with cAMP formation on the modulation of Ca(2+) spikes and neuronal excitability was examined. Forskolin, the activators of adenylate cyclase, suppressed afterhyperpolarization (AHP) and increased the activity of snail neurons without any significant effect on the Ca(2+) spike duration. Pretreatment with forskolin, although attenuated the suppressing effect of paraoxon on the duration of Ca(2+) spikes but also potentiated the paraoxon-induced hyperexcitability by enhancing the suppressive effects of paraoxon on AHP. Our findings support the possible involvement of cAMP formation in the paraoxon-induced AHP suppression and neuronal hyperexcitability, although activation of cAMP pathway may attenuates some effects of paraoxon.
authors.affiliation: Neuroscience Research Center, Department of Physiology, Faculty of Medicine, Shaheed Beheshti Medical Sciences University, PO Box 19835-181, Evin, Tehran, Iran.
authors.forename: Jafar
authors.initials: J
authors.lastname: Vatanparast
authors.forename: Mahyar
authors.initials: M
authors.lastname: Janahmadi
authors.forename: Ali Reza
authors.initials: AR
authors.lastname: Asgari
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000818:Animals; D020013:Calcium Signaling / Q000187:drug effects*; D005576:Colforsin / Q000494:pharmacology*; D000242:Cyclic AMP / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D004789:Enzyme Activation; D017952:Ganglia, Invertebrate / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D066298:In Vitro Techniques; D007306:Insecticides / Q000633:toxicity*; D008564:Membrane Potentials; D009474:Neurons / Q000187:drug effects* / Q000201:enzymology / Q000378:metabolism; D010261:Paraoxon / Q000633:toxicity*; D012908:Snails; D013997:Time Factors
chemical_list: D007306:Insecticides; D005576:Colforsin; D000242:Cyclic AMP; D000262:Adenylyl Cyclases; D010261:Paraoxon