Dopaminergic Modulation of GABAergic Transmission in the Entorhinal Cortex: Concerted Roles of alpha(1) Adrenoreceptors, Inward Rectifier K+, and T-Type Ca2+ Channels

作者：Cilz Nicholas I; Kurada Lalitha; Hu Binqi; Lei Saobo^*

来源：Cerebral Cortex, 2014, 24(12): 3195-3208.

DOI：10.1093/cercor/bht177

• depolarization
• entorhinal
• GABAA receptor
• interneuron
• synapse
• synaptic transmission

Whereas the entorhinal cortex (EC) receives profuse dopaminergic innervations from the midbrain, the effects of dopamine (DA) on gamma-Aminobutyric acid (GABA)ergic interneurons in this brain region have not been determined. We probed the actions of DA on GABA(A) receptor-mediated synaptic transmission in the EC. Application of DA increased the frequency, not the amplitude, of spontaneous IPSCs (sIPSCs) and miniature IPSCs (mIPSCs) recorded from entorhinal principal neurons, but slightly reduced the amplitude of the evoked IPSCs. The effects of DA were unexpectedly found to be mediated by alpha(1) adrenoreceptors, but not by DA receptors. DA endogenously released by the application of amphetamine also increased the frequency of sIPSCs. Ca2+ influx via T-type Ca2+ channels was required for DA-induced facilitation of sIPSCs and mIPSCs. DA depolarized and enhanced the firing frequency of action potentials of interneurons. DA-induced depolarization was independent of extracellular Na+ and Ca2+ and did not require the functions of hyperpolarization-activated (Ih) channels and T-type Ca2+ channels. DA-generated currents showed a reversal potential close to the K+ reversal potential and inward rectification, suggesting that DA inhibits the inward rectifier K+ channels (Kirs). Our results demonstrate that DA facilitates GABA release by activating a1 adrenoreceptors to inhibit Kirs, which further depolarize interneurons resulting in secondary Ca2+ influx via T-type Ca+ channels.

• 出版日期2014-12