title: Peptidergic excitation of supraoptic nucleus neurons: involvement of stretch-inactivated cation channels.
abstract: Although the primary stimulus regulating vasopressin (VP) release is a change in systemic osmolality, other physiological parameters are known to affect VP secretion or modulate the osmotic control over its release. Neuropeptides feature prominently in afferents underlying the central regulation of the VP-releasing magnocellular neurosecretory cells (MNCs). Although little is yet known of the circumstances under which peptides are released onto MNCs, previous studies have shown that a common response profile to exogenous peptide application is a slow excitation that seems to result from the activation of a nonselective cation conductance. In this paper we review the basis for the excitatory effects of angiotensin II, cholecystokinin, and neurotensin in MNCs acutely isolated from the supraoptic nucleus of adult rats. Saturating concentrations of these three peptides evoked nonadditive increases in macroscopic cation conductance. During single-channel recordings Ang II, CCK, and NT caused kinetically identical increases in the probability of opening of 35-pS nonselective cation channels. Patches containing only one channel further revealed that the activity of single channels could be regulated by separate applications of all three peptides. Peptide-stimulated channels were also found to be inactivated by increases in membrane stretch and to be blocked by low concentrations of gadolinium (Gd(3+)). It is concluded that many excitatory peptides depolarize MNCs by stimulating the stretch-inactivated cation channels underlying osmoreception. Convergent regulation of these channels provides a potentially powerful mechanism for integrating signals derived from the various afferents involved in the regulation of MNCs.
authors.affiliation: Centre for Research in Neuroscience, Montreal General Hospital and McGill University, 1650 Cedar Avenue, Montreal, QC, H3G 1A4, Canada.
authors.forename: Y
authors.initials: Y
authors.lastname: Chakfe
authors.forename: C W
authors.initials: CW
authors.lastname: Bourque
mesh_terms: D000804:Angiotensin II / Q000494:pharmacology; D000818:Animals; D002766:Cholecystokinin / Q000494:pharmacology; D007473:Ion Channels / Q000037:antagonists & inhibitors / Q000502:physiology*; D009474:Neurons / Q000187:drug effects / Q000502:physiology*; D009479:Neuropeptides / Q000502:physiology*; D009496:Neurotensin / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000187:drug effects / Q000502:physiology*; D014667:Vasopressins / Q000502:physiology
chemical_list: D007473:Ion Channels; D009479:Neuropeptides; D014667:Vasopressins; D000804:Angiotensin II; D009496:Neurotensin; D002766:Cholecystokinin