Voltage-dependence of glycine-activated Cl- channels: a potentiometer for inhibition?

Single- and double-electrode voltage-clamp techniques have been employed in situ to analyze Mauthner cell inhibitory synaptic responses produced both by activation of the recurrent collateral network and by direct intracellular stimulation of single presynaptic interneurons. The results demonstrate that the synaptically evoked glycinergic postsynaptic currents exhibit a striking voltage sensitivity. Specifically, the time constant of the decay of the synaptic conductance is increased by depolarization and decreased by hyperpolarization. This parameter is exponentially related to membrane potential, changing e-fold for a 45 mV potential shift, regardless of the degree of intracellular chloride loading or the magnitude of the underlying synaptic conductance. In addition, the amplitude of this inhibitory conductance change is decreased by membrane hyperpolarizations of 15 mV or more. Computer modeling demonstrates that the voltage dependence of the kinetics of the synaptic response may serve to enhance the magnitude and duration of inhibitory responses appreciably in the face of increased excitation.