Mechanism of long-lasting synaptic inhibition in Aplysia neuron R15.

1. Long-lasting inhibition is a synaptically mediated response found in certain molluscan nerve cells that fire action potentials in bursts. It is elicited by repetitive stimulation of a presynaptic nerve and may last for minutes or hours after stimulation. 2. Voltage-clamp techniques were employed to measure the voltage dependence of the synaptically elicited current. Current-voltage curves were obtained by stepping or sweeping the voltage over the range -40 to -120 mV. 3. Long-lasting inhibition was found to be mediated by two separate conductance mechanisms. A component that reverses near -80 mV is most prominent at times up to 5 min following stimulation. A component with no reversal potential between -40 and -120 mV predominates at later times. 4. The reversible component is attenuated by reducing the intensity of stimulation of the presynaptic nerve, by injection of TEA into the postsynaptic cell, or by activation of a potassium conductance with serotonin prior to stimulation of the nerve. Thus, the reversible component appears to be mediated by an increase in potassium conductance. 5. The effects of the nonreversible component measured in the soma appear to be too large to attribute it to a conductance change that is electrically "distant" from the soma. It is attenuated by turning off a resting inward ion conductance with dopamine prior to stimulation of the nerve. It is not affected by short exposure to ouabain, but is attenuated by longer exposures that reduce the sodium and calcium gradients. Thus, the nonreversible component may be mediated by a decrease in voltage-dependent inward current flow carried by sodium or calcium.