Ca2+-dependent inward current induced by nicotinic receptor activation depends on Ca2+/calmodulin-CaMKII pathway in dopamine neurons.
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.
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*
D004791:Enzyme Inhibitors; D011978:Receptors, Nicotinic; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D002118:Calcium; D004298:Dopamine