Vasopressin/oxytocin-related conopressin induces two separate pacemaker currents in an identified central neuron of Lymnaea stagnalis.

The molluscan vasopressin/oxytocin analogue Lys-conopressin excites neurons in the anterior lobe of the right cerebral ganglion of the snail Lymnaea stagnalis. Persistent inward currents that underlie the excitatory response were studied with the use of voltage-ramp protocols in the identified neuron RCB1 and other anterior lobe neurons. Under whole cell voltage-clamp conditions, two types of conopressin-activated current could be distinguished on the basis of their voltage dependence: 1) a pacemaker-like current that was activated at potentials above -40 mV (high-voltage-activated current, I(HVA)) and 2) an inward current that was activated at all potentials between -90 and +10 mV (low-voltage-activated current, I(LVA)). Ion substitution experiments indicate that sodium is the main charge carrier for I(HVA) and I(LVA). Both 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 desensitization and washout of I(HVA) and I(LVA) are different. The HVA response shows little desensitization, whereas the LVA response desensitizes within minutes (time constant 80 +/- 28 s, mean +/- SD). The time constant 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 conopressin receptors are involved in the activation of both currents. The conopressin-activated currents induce or enhance a region of negative slope resistance in the steady-state current-voltage relation. They differ from a third persistent inward current that is carried by calcium and completely blocked by cadmium. The presumed functional roles of these currents, possibly including autoregulation, are discussed.