Research PaperInward rectifier K+ channel and T-type Ca2 + channel contribute to enhancement of GABAergic transmission induced by β1-adrenoceptor in the prefrontal cortex

- Dobutamine enhances GABAergic transmission onto pyramidal neurons.
- T-type Ca2 + channel is involved in dobutamine-enhanced GABA release.
- Dobutamine depolarizates GABAergic interneurons through inhibition of Kir.

The functions of prefrontal cortex (PFC) are sensitive to norepinephrine (NE). Endogenously released NE influences synaptic transmission through activation of different subtypes of adrenergic receptors in PFC including α1, α2, β1 or β2-adrenoceptor. Our recent study has revealed that β1-adrenoceptor (β1-AR) activation modulates glutamatergic transmission in the PFC, whereas the roles of β1-AR in GABAergic transmission are elusive. In the current study, we probed the effects of the β1-AR agonist dobutamine (Dobu) on GABAergic transmission onto pyramidal neurons in the PFC of juvenile rats. Dobu increased both the frequency and amplitude of miniature IPSCs (mIPSCs). Ca2 + influx through T-type voltage-gated Ca2 + channel was required for Dobu-enhanced mIPSC frequency. We also found that Dobu facilitated GABA release probability and the number of releasable vesicles through regulating T-type Ca2 + channel. Dobu depolarized GABAergic fast-spiking (FS) interneurons with no effects on the firing rate of action potentials (APs) of interneurons. Dobu-induced depolarization of FS interneurons required inward rectifier K+ channel (Kir). Our results suggest that Dobu increase GABA release via inhibition of Kir, which further depolarizes FS interneurons resulting in Ca2 + influx via T-type Ca2 + channel.