Inhibitory postsynaptic currents of rat substantia nigra pars reticulata neurons: role of GABA receptors and GABA uptake

Abstract

Whole-cell patch-clamp recordings were made from substantia nigra pars reticulata neurons in midbrain slices of young rats to study the characteristics of spontaneous and evoked inhibitory postsynaptic currents and factors which govern their decay kinetics. In the presence of the glutamate receptor antagonists d, l-2-amino-5-phosphonopentanoic acid (20 μM) and 6-cyano-7-nitroquinoxaline-2,3-dione (20 μM), bicuculline-sensitive spontaneous inward inhibitory postsynaptic currents were often observed using high Cl − electrodes. Application of the selective GABA B receptor antagonist CGP55845A (2 μM) did not alter the half decay time of these inhibitory postsynaptic currents, which however was prolonged by the potent GABA uptake blocker tiagabine (1 μM). In addition, the frequencies and amplitudes of the inhibitory postsynaptic currents were significantly reduced by tiagabine but these effects were prevented by CGP55845A. Inhibitory postsynaptic currents with similar sensitivity to bicuculline could also be evoked intranigrally. Similar to the spontaneous currents, the decay time of evoked inhibitory postsynaptic currents was not affected by 2 μM CGP55845A. However, in the absence of CGP55845A, tiagabine shortened the IPSC decay time but had an opposite effect if CGP55845A was present. These data suggest that the spontaneous and evoked inhibitory postsynaptic currents recorded from substantia nigra pars reticulata neurons are mediated mainly by GABA A receptors. Uptake of GABA helps to terminate these currents. When the uptake mechanism is blocked, accumulation of GABA would lead to activation of presynaptic GABA B receptors and reduction in GABA release. The role of postsynaptic GABA B receptors in substantia nigra pars reticulata of young rats seems to be minimal.