Oxytocin retrogradely inhibits evoked, but not miniature, EPSCs in the rat supraoptic nucleus: role of N- and P/Q-type calcium channels.
We previously reported that oxytocin (OXT), released from the dendrites of magnocellular neurons in the supraoptic nucleus (SON), acts retrogradely on presynaptic terminals to inhibit glutamatergic transmission. Here we test the hypothesis that oxytocin reduces calcium influx into the presynaptic terminal. We used nystatin perforated-patch recording in vitro to first identify the calcium channels involved in glutamatergic transmission in the SON. [omega]-Conotoxin GVIA ([omega]-CTx) and [omega]-Agatoxin TK ([omega]-Aga) both reduced evoked EPSC amplitude, while nicardipine and nickel had no effect. A combination of [omega]-CTx and [omega]-Aga completely abolished the evoked EPSCs. This depressant effect was accompanied by an increase in the paired pulse ratio with no change in the kinetics of the evoked EPSCs, AMPA currents or postsynaptic cell properties. These results suggest that presynaptic N- and P/Q-type calcium channels mediate glutamate release in the SON while L-, T- and R-type channels make little or no contribution. Oxytocin-induced reduction of the evoked EPSC was substantially occluded in the presence of [omega]-CTx but only partially in the presence of [omega]-Aga. Amastatin, an endopeptidase inhibitor that increases the level of endogenous OXT, also reduced the evoked EPSC. This amastatin effect was also occluded by [omega]-CTx and [omega]-Aga. Miniature EPSCs, which are independent of extracellular calcium, were unaffected by either [omega]-CTx or by OXT, thus further substantiating an action of both compounds on calcium channels. Therefore, dendritically released oxytocin acts mainly via a mechanism involving the N-type channel, and to a lesser extent the P/Q-type channel, to decrease excitatory transmission.
Hirasawa
M
M
Neuroscience Research Group, Department of Physiology and Biophysics, University of Calgary, Calgary, Alberta, Canada. hirasawa@ucalgary.ca
Kombian
S B
SB
Pittman
Q J
QJ
D060848:Agatoxins; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020864:Calcium Channels, N-Type / Q000502:physiology*; D019706:Excitatory Postsynaptic Potentials / Q000187:drug effects* / Q000502:physiology; D018698:Glutamic Acid / Q000378:metabolism; D008297:Male; D010121:Oxytocin / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D017729:Presynaptic Terminals / Q000737:chemistry / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D013111:Spider Venoms / Q000494:pharmacology; D013495:Supraoptic Nucleus / Q000737:chemistry / Q000502:physiology*; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D060848:Agatoxins; D002118:Calcium; D002121:Calcium Channel Blockers; D020864:Calcium Channels, N-Type; D018698:Glutamic Acid; D010121:Oxytocin; D013111:Spider Venoms; D020866:omega-Conotoxin GVIA; C083855:omega-agatoxin-Aa4b