VASOPRESSIN OXYTOCIN-RELATED CONOPRESSIN INDUCES 2 SEPARATE PACEMAKERCURRENTS IN AN IDENTIFIED CENTRAL NEURON OF LYMNAEA-STAGNALIS/

The molluscan vasopressin/oxytocin analogue Lys-conopressin excites ne urons in the anterior lobe of the right cerebral ganglion of the snail Lymnaea stagnalis. Persistent inward currents that underlie the excit atory response were studied with the use of voltage-ramp protocols in the identified neuron RCB1 and other anterior lobe neurons. Under whol e cell voltage-clamp conditions, two types of conopressin-activated cu rrent could be distinguished on the basis of their voltage dependence: I) a pacemaker-like current that was activated at potentials above -4 0 mV (high-voltage-activated current, I-HVA) and 2) an inward current that was activated at all potentials between -90 and +10 mV (low-volta ge-activated current, I-LVA) Ion substitution experiments indicate tha t sodium is the main charge carrier for I-HVA and I-LVA Bath currents are differentially affected by cadmium. I-HVA and I-LVA differ in dose dependence, with median effective concentration values of 7.7 x 10(-8 ) M and 2.2 x 10(-7) M, respectively. Vasopressin and oxytocin act as weak agonists for the conopressin responses. The kinetics of desensiti zation and washout of I-HVA and I-LVA are different. The HVA response shows little desensitization, whereas the LVA response desensitizes wi thin minutes (time constant 80 +/- 28 s, mean +/- SD). The time consta nt of washout on removal of conopressin is 159 +/- 63 s for I-HVA and 36 +/- 13 s for I-LVA. These results suggest that two distinct conopre ssin receptors are involved in the activation of both currents. The co nopressin-activated currents induce or enhance a region of negative sl ope resistance in the steady-state current-voltage relation. They diff er from a third persistent inward current that is carried by calcium a nd completely blocked by cadmium. The presumed functional roles of the se currents, possibly including autoregulation, are discussed.