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Local Application of Drugs to Study Nicotinic Acetylcholine Receptor Function in Mouse Brain Slices
Published on: October 29, 2012
Fulfenamic acid sensitive, Ca(2+)-dependent inward current induced by nicotinic acetylcholine receptors in dopamine
Tetsuji Yamashita1, Tadashi Isa
1Department of Integrative Physiology, National Institute for Physiological Sciences and Graduate University for Advanced Studies, Myodaiji, Okazaki 444-8585, Japan.
Abstract:
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.
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