Vasopressin's depolarizing action on neonatal rat spinal lateral horn neurons may involve multiple conductances

Abstract

Vasopressin-immunoreactive fibers have been visualized in the area of spinal lateral horn cells, including spinal sympathetic preganglionic neurons (SPNs). The presence and nature of vasopressin receptors on 125 neurons in this area were addressed using whole-cell patch-clamp techniques in transverse spinal cord slice preparations from neonatal rat (11-21 days). Local pressure applications of Arg8-vasopressin (AVP, 1 μM) induced a slow- onset membrane depolarization accompanied by spike discharges and membrane oscillations. In voltage-clamp, applications of AVP (10nM-1 μM) induced a reversible, tetrodotoxin-resistant and dose-dependent inward current in 90% of tested cells. This effect was blocked by a V1 receptor antagonist [D- (CH2)5 Tyr (Me)-AVP], whereas a V2 receptor agonist [desamino-(D-Arg8)- vasopressin] was ineffective. Both the amplitude and duration of the AVP effect were significantly modified after intracellular dialysis of non- hydrolysable G-protein modulators. I-V relationships, examined in 75 cells, suggested two conductances. In 36 cells the net AVP current reversed ~- 102mV, was associated with a decrease in membrane conductance and yielded linear I-V plots, suggesting mediation through closure of a resting potassium conductance. In a further 26 cells the I-V lines remained almost parallel in the voltage range used in this study (-130 to -40mV), while the membrane conductance was decreased in a majority of these cells. In the remaining 13 cells the net AVP current was estimated to reverse ~-30mV and was associated with a small increase in membrane conductance, suggesting mediation through opening of a non-selective cationic conductance. These data indicate that the majority of SPNs and other lateral horn cells possess functional G-protein- coupled V1-type vasopressin receptors in the neonatal spinal cord. In the adult spinal cord, some of these receptors are likely to participate in CNS regulation of autonomic nervous system function.