title: Ca2+-dependent inward current induced by nicotinic receptor activation depends on Ca2+/calmodulin-CaMKII pathway in dopamine neurons.
abstract: It is well known that midbrain dopamine (DA) neurons receive massive projection from cholinergic neurons in the brainstem. In our preceding report, we showed that Ca(2+)-influx through nicotinic acetylcholine (ACh) receptors in the DA neurons subsequently activated an inward current that was sensitive to fulfenamic acid (FFA) and phenytoin, presumably a Ca(2+)-activated non-selective cation current. The FFA-sensitive current exhibited a negative slope conductance and predominantly enhanced the depolarizing responses of DA neurons. In this study, we showed that the inward FFA-sensitive current was eliminated by antagonists of Ca(2+)/calmodulin (Ca(2+)/CaM), N-(6-aminohexyl)-5-chloro-1-naphthalene-sulfonamide hydrochloride (W-7; 1 microM), trifluoperazine (TFP; 1.5 microM) and calmidazolium (100 nM). Application of W-7 and TFP reduced the ACh-induced inward current and the current component suppressed by these drugs exhibited negative slope conductance, as well as the FFA-sensitive current. Further, intracellular application of KN-93, an antagonist of Ca(2+)/CaM-dependent protein kinase II (CaMKII), but not KN-92 eliminated the FFA-sensitive current. All these results suggest that Ca(2+)/CaM-CaMKII pathway is involved in an activation of the FFA-sensitive current.
mesh_terms: D000818:Animals; D002118:Calcium / Q000502:physiology*; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000037:antagonists & inhibitors / Q000502:physiology*; D004298:Dopamine / Q000502:physiology*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D066298:In Vitro Techniques; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D011978:Receptors, Nicotinic / Q000502:physiology*; D015398:Signal Transduction / Q000187:drug effects / Q000502:physiology*
chemical_list: D004791:Enzyme Inhibitors; D011978:Receptors, Nicotinic; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D004298:Dopamine