Forskolin attenuates the paraoxon-induced hyperexcitability in snail neurons

Introduction: Since organophosphorus compounds (OP) are toxic and designed to destroy insects and pest species, there are many hazards associated with their use. Although, the main target site of these compounds is acetylcholinesterase (AChE), however it has become increasingly evident that OPs have also other direct effects on cellular processes. In the present study, the effects of low concentrations of paraoxon and its interaction with forskolin, an activator of protein kinase A (PKA), were studied on Ca2+ spike configuration and frequency in neurons of snail Caucasotachea atrolabiata. Methods: Subesophageal ganglia neurons were recorded in current clamp mode in Na+ free Ringer solution that contained voltage dependent potassium channel blockers, 4AP and TEA. Results: Paraoxon (0.3-0.6 μM) decreased the duration of spontaneous Ca2+ spikes. This effect was seen with a suppression of single spike AHPs, leading to an increment in firing rate. Paraoxon induced hyperactivity appeared to be a consequence of decrease in Ca2+ influx during spikes which is the main determinant of AHP duration by activating Ca2+ dependent potassium channels. Forskolin (25 μM), in the absence of a significant change in spike duration, decreased the duration of single spike AHPs and increased the frequency of spikes. After forskolin application, paraoxon decreased the duration of Ca2+ spikes and AHPs, and increased the activity. However, these effects, especially on spike duration, were not as pronounced as in the absence of forskolin. Conclusion: These findings suggest that although forskolin, similar to paraoxon, decreases the AHP and increases the frequency of spikes but it employs mechanism(s) different from paraoxon which also oppose the effects of paraoxon on Ca2+ spikes configuration and frequency.