CONOPRESSIN AFFECTS EXCITABILITY, FIRING, AND ACTION-POTENTIAL SHAPE THROUGH STIMULATION OF TRANSIENT AND PERSISTENT INWARD CURRENTS IN MULLUSCAN NEURONS

The molluscan vasopressin/oxytocin-related neuropeptide conopressin ac tivates two persistent inward currents in neurons from the anterior lo be of the right cerebral ganglion of Lymnaea stagnalis that are involv ed in the control of male copulatory behavior. The low-voltage-activat ed (LVA) current is activated at a wide range of membrane potentials, its amplitude being only weakly voltage dependent. The high-voltage-ac tivated (HVA) current is activated at potentials positive to -40 mV on ly and shows a steep voltage dependence. Occurrence of both currents v aries from cell to cell, some expressing both and others only the HVA current. In most neurons that have the LVA current, a conopressin-inde pendent persistent inward current (I-NSR) is found that resembles the KVA current in its voltage dependence. The functional importance of th e LVA and HVA currents was studied under current-clamp conditions in i solated anterior lobe neurons. In cells exhibiting both current types, the effect of activation of the LVA. current alone was investigated a s follows: previously recorded LVA current profiles were injected into the neurons, and the effects were compared with responses induced by conopressin. Both treatments resulted in a strong depolarization and f iring activity. No differences in firing frequency and burst duration were observed, indicating that activation of the LVA current is suffic ient to evoke bursts. In cells exhibiting only the HVA current, the ef fect of conopressin on the response to a depolarizing stimulus was tes ted. Conopressin reversibly increased the number of action potentials generated by the stimulus, suggesting that the HVA current enhances ex citability and counteracts accommodation. Conopressin enhanced action potential broadening during depolarizing stimuli in many neurons. Volt age-clamp experiments performed under ion-selective conditions reveale d the presence of transient sodium and calcium currents. Using the act ion potential clamp technique, it was shown that both currents contrib ute to the action potential. The calcium current, which is activated m ainly during the repolarizing phase of the action potential, is augmen ted by conopressin. Thus conopressin may directly modulate the shape o f the action potential. In summary, conopressin may act simultaneously on multiple inward currents in anterior lobe neurons of Lymnaea to af fect firing activity, excitability, and action potential shape.