Peptidergic excitation of supraoptic nucleus neurons: Involvement of stretch-inactivated cation channels

Although the primary stimulus regulating vasopressin (VP) release is a chan ge in systemic osmolality, other physiological parameters are known to affe ct VP secretion or modulate the osmotic control over its release. Neuropept ides feature prominently in afferents underlying the central regulation of the V-P-releasing magnocellular neurosecretory cells (MNCs). Although littl e is yet known of the circumstances under which peptides are released onto MNCs, previous studies have shown that a common response profile to exogeno us peptide application is a slow excitation that seems to result from the a ctivation of a nonselective cation conductance. In this paper we review the basis for the excitatory effects of angiotensin H, cholecystokinin, and ne urotensin in MNCs acutely isolated from the supraoptic nucleus of adult rat s. Saturating concentrations of these three peptides evoked nonadditive inc reases in macroscopic cation conductance. During single-channel recordings Ang II, CCK, and NT caused kinetically identical increases in the probabili ty of opening of 35-pS nonselective cation channels. Patches containing onl y one channel further revealed that the activity of single channels could b e regulated by separate applications of all three peptides. Peptide-stimula ted channels were also found to be inactivated by increases in membrane str etch and to he blocked by low concentrations of gadolinium (Gd3+). It is co ncluded that many excitatory peptides depolarize MNCs by stimulating the st retch-inactivated cation channels underlying osmoreception. Convergent regu lation of these channels provides a potentially powerful mechanism for inte grating signals derived from the various afferents involved in the regulati on of MNCs. (C) 2001 Academic Press.