Ivermectin potentiates ATP-induced ion currents in cortical neurones: evidence for functional expression of P2X4 receptors?
We examined the effects of an antiparasitic agent ivermectin on ATP- and alpha,beta-methylene-ATP (alpha,beta-me-ATP)-activated currents in neurones acutely isolated from slices of somato-sensory cortex of 17-22 days old CBL57 mice. Membrane currents were monitored using whole-cell patch clamp combined with a "concentration-clamp" fast agonist application system. Ivermectin potentiated membrane currents induced by both ATP and alpha,beta-me-ATP applied alone or in the presence of broad P2X antagonist PPADS. Ivermectin also significantly increased amplitude and frequency of spontaneous P2X-mediated EPSCs recorded from cortical slices incubated with mixture of glutamate (CNQX, D-APV, SYM2081), GABA (picrotoxin), nicotinic cholinoreceptor (hexamethonium) antagonists and sodium channel blocker tetrodotoxin. These results indicate functional expression of P2X4 receptors in cortical neurones and their involvement in purinergic synaptic transmission in cortex.
Lalo
Ulyana
U
Faculty of Medicine, Imperial College, London W12 0 NN, UK.
Verkhratsky
Alexei
A
Pankratov
Yuri
Y
D000255:Adenosine Triphosphate / Q000031:analogs & derivatives / Q000494:pharmacology*; D000818:Animals; D000831:Animals, Newborn; D000970:Antineoplastic Agents / Q000494:pharmacology; D002540:Cerebral Cortex / Q000166:cytology*; D004305:Dose-Response Relationship, Drug; D004347:Drug Interactions; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects; D007306:Insecticides / Q000494:pharmacology*; D007559:Ivermectin / Q000494:pharmacology*; D008564:Membrane Potentials / Q000187:drug effects*; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000187:drug effects*; D018408:Patch-Clamp Techniques; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology; D011732:Pyridoxal Phosphate / Q000031:analogs & derivatives / Q000494:pharmacology
D000970:Antineoplastic Agents; D007306:Insecticides; D010975:Platelet Aggregation Inhibitors; C077792:pyridoxal phosphate-6-azophenyl-2',4'-disulfonic acid; D011732:Pyridoxal Phosphate; D007559:Ivermectin; D000255:Adenosine Triphosphate; C002630:alpha,beta-methyleneadenosine 5'-triphosphate