The involvement of voltage-operated calcium channels in somato-dendritic oxytocin release.
Magnocellular neurons of the supraoptic nucleus (SON) secrete oxytocin and vasopressin from axon terminals in the neurohypophysis, but they also release large amounts of peptide from their somata and dendrites, and this can be regulated both by activity-dependent Ca(2+) influx and by mobilization of intracellular Ca(2+). This somato-dendritic release can also be primed by agents that mobilise intracellular Ca(2+), meaning that the extent to which it is activity-dependent, is physiologically labile. We investigated the role of different Ca(2+) channels in somato-dendritic release; blocking N-type channels reduced depolarisation-induced oxytocin release from SONs in vitro from adult and post-natal day 8 (PND-8) rats, blocking L-type only had effect in PND-8 rats, while blocking other channel types had no significant effect. When oxytocin release was primed by prior exposure to thapsigargin, both N- and L-type channel blockers reduced release, while P/Q and R-type blockers were ineffective. Using confocal microscopy, we found immunoreactivity for Ca(v)1.2 and 1.3 channel subunits (which both form L-type channels), 2.1 (P/Q type), 2.2 (N-type) and 2.3 (R-type) in the somata and dendrites of both oxytocin and vasopressin neurons, and the intensity of the immunofluorescence signal for different subunits differed between PND-8, adult and lactating rats. Using patch-clamp electrophysiology, the N-type Ca(2+) current density increased after thapsigargin treatment, but did not alter the voltage sensitivity of the channel. These results suggest that the expression, location or availability of N-type Ca(2+) channels is altered when required for high rates of somato-dendritic peptide release.
Centre for Integrative Physiology, University of Edinburgh, Edinburgh, United Kingdom.
Vicky A
VA
Tobin
Alison J
AJ
Douglas
Gareth
G
Leng
Mike
M
Ludwig
D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D003712:Dendrites / Q000187:drug effects / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007774:Lactation / Q000378:metabolism; D010121:Oxytocin / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013495:Supraoptic Nucleus / Q000166:cytology; D019284:Thapsigargin / Q000494:pharmacology; D014667:Vasopressins / Q000378:metabolism
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D014667:Vasopressins; D010121:Oxytocin; D019284:Thapsigargin; D002118:Calcium