Properties of isolated GABA B-mediated inhibitory postsynaptic currents in hippocampal pyramidal cells

Abstract

Whole-cell recording techniques were used to record isolated slow inhibitory postsynaptic currents in CA1 pyramidal neurons from rat hippocampal slices. Application of 6-cyano-7-nitroquinoxaline-2,3-dione and 3-(2-car☐ypiperazin-4-yl)propyl-1-phosphonic acid eliminated excitatory synaptic transmission, resulting in a 38% reduction in slow inhibitory postsynaptic current magnitude. Subsequent addition of the GABA A antagonist picrotoxin caused a further decrease in slow inhibitory postsynaptic current amplitude. The remaining, isolated slow inhibitory postsynaptic current was blocked by the GABA B antagonist 2-hydroxysaclofen and when cesium was substituted for intracellular potassium. The kinetics of isolated slow inhibitory postsynaptic currents were characterized by single exponential, fourth power activation, and double exponential inactivation. These slow inhibitory postsynaptic currents had a reversal potential of−85.7 ± 1.6mV, and a slope conductance of935 ± 277pS. Single slow inhibitory postsynaptic currents carried a total charge flux of13.4 ± 7.6pC. Repetitive stimulation up to 1 Hz progressively reduced steady-state slow inhibitory postsynaptic current amplitude. This attenuation was characterized by a decrease in slope conductance, but slow inhibitory postsynaptic current reversal potential remained unchanged, as did slow inhibitory postsynaptic current kinetics. These results indicate that, under physiological conditions, both ionotropic glutamate- and GABA A-mediated transmission contribute to slow inhibitory postsynaptic current recruitment. Given this finding, activity-dependent decreases in GABA A transmission could contribute to slow inhibitory postsynaptic current depression, though not exclusively, since isolated slow inhibitory postsynaptic currents also demonstrated this property. The use-dependent depression of isolated slow inhibitory postsynaptic currents may be a consequence of a reduction in transmitter release.