thapsigargicin and biocytin

Nicotinic acetylcholine receptors (nAChRs) exhibit high Ca(2+) permeabilities and the Ca(2+)-influx through the nAChRs may be involved in regulation of a variety of signal processing in the postsynaptic neurons. The mesencephalic dopamine (DA) neurons receive cholinergic inputs from the brainstem and express abundant nAChRs. Here we report that the Ca(2+)-influx induced by a transient pressure application of ACh activates an inward current mediated by nAChRs and subsequently an inward current component that is sensitive to fulfenamic acid (FFA) and phenytoin, presumably a Ca(2+)-activated nonselective cation current in the DA neurons in the midbrain slices of the rat. The FFA- and phenytoin-sensitive current exhibits a negative slope conductance below -40 mV, suggesting its role in significant enhancement of depolarizing responses. In the current clamp recordings with perforated patch clamp configuration, bath application of carbachol markedly enhanced the glutamate-induced depolarization, which led to a long-lasting depolarizing hump. Activation of nAChRs is involved in this process, in cooperation with muscarinic receptors that suppress afterhyperpolarization caused by Ca(2+)-activated K(+)-channels. The long-lasting depolarizing hump was suppressed by FFA. All these results suggested a potential role of the FFA-sensitive current triggered by nAChR activation in marked enhancement of the excitatory synaptic response in DA neurons.

Topics: Acetates; Animals; Animals, Newborn; Anti-Inflammatory Agents, Non-Steroidal; Anticonvulsants; Atropine; Calcium; Carbachol; Chelating Agents; Chlorides; Cholinergic Agonists; Dopamine; Dose-Response Relationship, Drug; Drug Interactions; Egtazic Acid; Electric Conductivity; Flufenamic Acid; Glutamic Acid; In Vitro Techniques; Lactones; Lysine; Mecamylamine; Membrane Potentials; Muscarinic Antagonists; Neurons; Nicotinic Antagonists; Patch-Clamp Techniques; Phenytoin; Rats; Rats, Wistar; Receptors, Nicotinic; Sesquiterpenes; Substantia Nigra; Ventral Tegmental Area