Dopamine inhibits N‐type channels in chemosensory afferents to reduce synaptic transmitter release under normoxic and chronic intermittent hypoxic (CIH) conditions

Abstract

Evoked synaptic currents elicited in second‐order neurons in the nucleus of the solitary tract (nTS) by activation of chemoafferent fibers are reduced after 10 days of CIH. The mechanism by which this occurs is unknown. One candidate is dopamine (DA) which is released from the presynaptic terminal and exerts a tonic presynaptic inhibition on glutamate release. We postulated that 1) tonic activation of D2 receptors inhibit presynaptic calcium currents to reduce transmitter release and 2) this occurs to a greater extent in CIH. Experiments were performed in isolated nodose‐petrosal cells to examine calcium currents and nTS slices to study presynaptic calcium fluorescence and synaptic currents. DA and quinpirole (Quin, D2 agonist) inhibited calcium currents by acting on the N‐type calcium channel under normoxic and CIH conditions. Quin also decreased the change in presynaptic terminal calcium fluorescence to solitary tract stimulation in nTS slices, an effect which occurred through inhibition of N‐type calcium channels. Yet in nTS slices from CIH animals, although the D2 antagonist sulpiride increased the CIH‐reduced amplitude of synaptic currents, EPSCs were not restored to normal levels. This indicates that while the DA inhibitory effect on calcium currents remains intact in CIH, most of the reduction in synaptic currents occurs via alternative mechanisms. NS52142 (RCR), HL085108 (DDK) and HL25830 (DLK).