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Volume 17, Number 19, Issue of October 1, 1997 pp. 7220-7227
Copyright ©1997 Society for Neuroscience

Properties of GABA_A Receptors Underlying Inhibitory Synaptic Currents in Neocortical Pyramidal Neurons

Received May 15, 1997; revised June 30, 1997; accepted July 10, 1997.

Mario Galarreta and Shaul Hestrin

Department of Anatomy and Neurobiology, College of Medicine, University of Tennessee, Memphis, Tennessee 38163

Rapid applications of GABA (from 10 µM to 10 mM) to outside-out patches were used to study the role that the kinetic properties of GABA_A receptors play in determining the time course of IPSCs in neocortical pyramidal neurons. Currents induced by rapid applications of brief (1 msec) pulses of GABA (1 mM) showed a biexponential decay phase that seems to involve the entry of GABA_A receptors into desensitized states. This conclusion is based on the similar fast decay kinetics of the response to brief and prolonged pulses of GABA and on the correlation between the degree of paired-pulse depression and the decay rate of the currents induced by brief pulses.

Under nonequilibrium conditions we found that the concentration-response curve of pyramidal GABA_A receptors has an EC₅₀ of 185 µM (GABA pulse of 1 msec). The decay time course of the patch currents in response to brief applications of GABA was insensitive to agonist concentrations at the range from 50 µM to 10 mM. Faster decay rates were observed only in response to pulses of 10 µM GABA. These data are compatible with the suggestion that briefer openings derive from a monoliganded state and that these are negligible when receptor activation is >2%. Assuming that GABA transients at neocortical synapses are fast, a several millimolar GABA concentration would be needed to saturate the postsynaptic GABA_A receptors.

Key words: cerebral cortex; inhibitory synapse; GABA; GABA_A receptor; desensitization; saturation; inhibition; rapid agonist application; pyramidal neuron; synaptic transmission; miniature IPSC

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