Opening of KATP Channel Regulates Tonic Currents From Pyramidal Neurons in Rat Brain.

Abstract

ATP-sensitive K+ (KATP) channels couple metabolic state to cellular excitability. Activation of neuronal and astrocytic mitochondrial KATP (mitoKATP) channels regulates a variety of neuronal functions. However, less is known about the impact of mitoKATP on tonic γ-aminobutyric acid (GABA) inhibition. Tonic GABA inhibition is mediated by the binding of ambient GABA on extrasynaptic GABA A-type receptors (GABAARs) and is involved in regulating neuronal excitability. We determined the impact of activation of KATP channels with diazoxide (DIZ) on tonic inhibition and recorded tonic current from rat cortical layer 5 pyramidal cells by patch-clamp recordings. We found that neonatal tonic current increased with an increase in GABA concentration, which was partially mediated by the GABA A-type receptor (GABAAR) α5, and likely the δ subunits. Activation of KATP channels resulted in decreased tonic current in newborns, but there was increased tonic current during the second postnatal week. These findings suggest that activation of KATP channels with DIZ regulates GABAergic transmission in neocortical pyramidal cells during development.