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Magnocellular oxytocin (OT) and vasopressin (VP) neurons express an afterhyperpolarization (AHP) following spike trains that attenuates firing rate and contributes to burst patterning. This AHP includes contributions from an apamin-sensitive, medium-duration AHP (mAHP) and from an apamin-insensitive, slow-duration AHP (sAHP). These AHPs are Ca 2+  dependent and activated by Ca 2+  influx through voltage-gated Ca 2+  channels. Across central nervous system neurons that generate Ca 2+ -dependent AHPs, the Ca 2+  channels that couple to the mAHP and sAHP differ greatly, but for magnocellular neurosecretory cells this relationship is unknown. Using simultaneous whole cell recording and Ca 2+  imaging, we evaluated the effect of specific high-voltage-activated (HVA) Ca 2+  channel blockers on the mAHP and sAHP. Block of all HVA channels via 400 μM Cd 2+  inhibited almost the entire AHP. We tested nifedipine, conotoxin GVIA, agatoxin IVA, and SNX-482, specific blockers of L-, N-, P/Q-, and R-type channels, respectively. The N-type channel blocker conotoxin GVIA (1 μM) was the only toxin that inhibited the mAHP in either OT or VP neurons although the effect on VP neurons was weaker by comparison. The sAHP was significantly inhibited by N-type block in OT neurons and by R-type block in VP neurons although neither accounted for the entirety of the sAHP. Thus the mAHP appears to be elicited by Ca 2+  from mostly N-type channels in both OT and VP neurons, but the contributions of specific Ca 2+  channel types to the sAHP in each cell type are different. Alternative sources to HVA channels may contribute Ca 2+  for the sAHP.    NEW &amp; NOTEWORTHY Despite the importance of afterhyperpolarization (AHP) mechanisms for regulating firing behavior of oxytocin (OT) and vasopressin (VP) neurons of supraoptic nucleus, which types of high-voltage-activated Ca 2+  channels elicit AHPs in these cells was unknown. We found that N-type channels couple to the medium AHP in both cell types. For the slow AHP, N-type channels contribute in OT neurons, whereas R-type contribute in VP neurons. No single Ca 2+  channel blocker abolished the entire AHP, suggesting that additional Ca 2+  sources are involved.

journal of neurophysiology

Specificity in the interaction of high-voltage-activated Ca2+ channel types with Ca2+-dependent afterhyperpolarizations in magnocellular supraoptic neurons