title: Expression of CaV 2.2 and splice variants of CaV 2.1 in oxytocin- and vasopressin-releasing supraoptic neurones.
abstract: The magnocellular neurosecretory cells (MNCs) release vasopressin (VP) and oxytocin (OT) from their axon terminals into the circulation and from their somata and dendrites to exert paracrine effects on other MNCs. MNCs express several types of voltage-gated Ca(2+) channels, including Ca(V)2.1 and Ca(V)2.2. These two channels types are similar in structure and function in other cells, but although influx of Ca(2+) through Ca(V)2.2 triggers the release of both OT and VP into the circulation, Ca(V)2.1 is involved in stimulating the release of VP but not OT. Release of OT from MNC somata is also triggered by Ca(V)2.2 but not Ca(V)2.1. These observations could be explained by differences in the level of expression of Ca(V)2.1 in VP and OT MNCs or by differences in the way that the two channels interact with the exocytotic apparatus. We used immunohistochemistry to confirm earlier work suggesting that MNCs express variants of Ca(V)2.1 lacking portions of an internal loop that enables the channels to interact with synaptic proteins. We used an antibody that would recognise both the full-length Ca(V)2.1 and the deletion variants to show that OT MNCs express fewer Ca(V)2.1 channels than do VP MNCs in both somata and axon terminals. We used the reverse transcriptase-polymerase chain reaction and immunocytochemistry to test whether MNCs express similar deletion variants of Ca(V)2.2 and were unable to find any evidence to support this. Our data suggest that the different roles that Ca(V)2.1 and Ca(V)2.2 play in MNC secretion may be a result of the different levels of expression of Ca(V)2.1 in VP and OT MNCs, as well as the expression in MNCs of deletion variants of Ca(V)2.1 that do not interact with exocytotic proteins and therefore may be less likely to mediate exocytotic release.
authors.affiliation: Department of Physiology, College of Medicine, University of Saskatchewan, Saskatoon, Canada.
authors.forename: D
authors.initials: D
authors.lastname: Wang
authors.forename: T E
authors.initials: TE
authors.lastname: Fisher
mesh_terms: D000818:Animals; D020864:Calcium Channels, N-Type / Q000235:genetics / Q000378:metabolism*; D008297:Male; D009474:Neurons / Q000378:metabolism*; D010121:Oxytocin / Q000378:metabolism; D012326:RNA Splicing; D051381:Rats; D020318:Rats, Long-Evans; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013495:Supraoptic Nucleus / Q000166:cytology / Q000378:metabolism*; D014667:Vasopressins / Q000378:metabolism*
chemical_list: D020864:Calcium Channels, N-Type; D010121:Oxytocin; D014667:Vasopressins; C503279:Cacna1b protein, rat
keywords: Ca2+ channels; oxytocin; splice variants; supraoptic; vasopressin