Inhibition of subfornical organ neuronal potassium channels by vasopressin

The subfornical organ is one of a specialized group of CNS structures devoi d of a significant blood-brain barrier, collectively known as the circumven tricular organs. While peptides are normally excluded from access to most r egions of the CNS, the subfornical organ contains neurons with a high densi ty of receptors for many circulating peptides, including vasopressin. There is a well-established role for the subfornical organ in stimulating the re lease of vasopressin, and recent evidence suggests that it may also play an important role in mediating the negative feedback actions of vasopressin. The aim of this study was to determine the direct effects of vasopressin on subfornical organ neurons through patch-clamp studies in a dissociated sub fornical organ preparation. In current-clamp studies, bath application of 1 0 nM vasopressin caused depolarizations in 61%, hyperpolarizations in 11%, and no significant change in membrane potential in 28% of neurons tested. W e then sought to determine the specific ion channels involved in regulating the vasopressin-induced excitability of subfornical organ neurons through voltage-clamp studies. Vasopressin (10 nM) decreased the peak outward curre nt at +40 mV by 50% (n=7), which was blocked by pretreatment with a V-1 rec eptor antagonist (n=5). Based on these findings, we carried out a systemati c characterization of two subfornical organ K+ channels, the delayed rectif ier (I-K) and the transient outward current (I-A) Through voltage isolation of IK, We found that vasopressin inhibited the steady-state current, by 33 +/-7% (n=9). Vasopressin also inhibited the peak IA by 27+/-5% (n=8). These data provide the first evidence of a role for K+ channels in mediatin g the excitatory effects of vasopressin on subfornical organ neurons. The e xact physiological roles and sources of vasopressin which may act on subfor nical organ neurons are not completely understood at present. (C) 1999 IBRO . Published by Elsevier Science Ltd.