A Voltage- and Activity-dependent Chloride Conductance Controls the Resting Status of the Intact Rat Sympathetic Neuron

Remarkable activity-dependence was uncovered in the chloride conductance that operates in the subthreshold region of membrane potential, by using the twomicroelectrode voltage-clamp technique in the mature and intact rat sympathetic neuron. Both direct and synaptic neuron tetanization (15 Hz, 10 s duration to saturate the response) resulted in a long-lasting (not less than 15 min) increase of cell input conductance (+70150% 10 min after tetanus), accompanied by the onset of an inward current with the same time course. Both processes developed with similar properties in the postganglionic neuron when presynaptic stimulation was performed under currentor voltage-clamp conditions, and were unaffected by external calcium upon direct stimulation. The posttetanic effects were sustained by gCl increase since both conductance and current modifications were blocked by 0.5 mM 9AC (a chloride channel blocker) but were unaffected by TEACl or cesium chloride treatments. The chloride channel properties were modified by stimulation: their voltage sensitivity and rate of closure in response to hyperpolarization strongly increased. The voltage dependence of the three major conductances governing the cell subthreshold status (gCl, gK and gL) was evaluated over the -40/-110 mV membrane potential range in unstimulated neurons and compared with previous results in stimulated neurons. A drastic difference between the voltage-conductance profiles was observed, exclusively sustained by gCl increase. The chloride channel thus hosts an intrinsic mechanism, a memory of previous neuron activity, which makes the chloride current a likely candidate for natural controller of the balance between opposite resting currents, and thus of membrane potential level.