Abstract
In some nerve cells, synaptically released GABA acting on postsynaptic GABAA receptor produce not only phasic inhibition, but also tonic inhibition by persistent activation of extrasynaptic receptors. However, functional consequences of the tonic GABAA receptor activation are not well understood. We performed patch clamp experiments, using a CsCl based pipette solution, in the neocortical layer V pyramidal cells of brain slices taken from P28-40 rats. GABAA receptor mediated currents were isolated by application of CNQX, APV, CGP55845 and TTX at 32 °C. Bath application of GABAA receptor antagonist bicuculline blocked miniature IPSCs (mIPSCs) and outwardly shifted baseline holding current (Ihold). SR95531, a GABAA receptor antagonist selective for phasic inhibition, similarly abolished mIPSCs but had no significant effect on Ihold. Thus, this tonic current was not a summation of mIPSCs attributable to the GABAA receptor activation. Bath application of benzodiazepines such as midazolam produced inward tonic currents. These currents are also abolished by bicuculline but not by SR95531, indicating benzodiazepine augmentation of the tonic GABAA receptor mediated current. These tonic currents are also abolished by bicuculline but not by SR95531, indicating benzodiazepine augmentation of the tonic GABAA receptor mediated current. Therefore, the tonic GABAA receptor mediated inhibition also might be regulating neocortical excitability, allowing a future studies to investigate its specific role in neuronal function. [Jpn J Physiol 54 Suppl:S147 (2004)]
