Enhancement of calcium‐dependent afterpotentials in oxytocin neurons of the rat supraoptic nucleus during lactation

Abstract

The firing pattern of oxytocin (OT) hormone synthesizing neurons changes dramatically immediately before each milk ejection, when a brief burst of action potentials is discharged. OT neurons possess intrinsic currents that would modulate this burst. Our previous studies showed the amplitude of the Ca 2+ -dependent afterhyperpolarization (AHP) following spike trains is significantly larger during lactation. In the present study we sought to determine which component of the AHP is enhanced, and whether the enhancement could be related to changes in whole-cell Ca 2+ current or the Ca 2+ transient in identified OT or vasopressin (VP) neurons during lactation. We confirmed, with whole-cell current-clamp recordings, our previous finding from sharp electrodes that the size of the AHP following spike trains increased in OT, but not VP neurons during lactation. We then determined that an apamin-sensitive medium-duration AHP (mAHP) and an apamin-insensitive slow AHP (sAHP) were specifically increased in OT neurons. Simultaneous Ca 2+ imaging revealed that the peak change in somatic [Ca 2+ ] i was not altered in either cell type, but the slow decay of the Ca 2+ transient was faster in both cell types during lactation. In voltage clamp, the whole-cell, Ca 2+ current was slightly larger during lactation in OT cells only, but current density was unchanged when corrected for somatic hypertrophy. The currents, I mAHP and I sAHP , also were increased in OT neurons only, but only the apamin-sensitive I mAHP showed an increase in current density after adjusting for somatic hypertrophy. These findings suggest a specific modulation (e.g. increased number) of the small-conductance Ca 2+ -dependent K + (SK) channels, or their interaction with Ca 2+ , underlies the increased mAHP/I mAHP during lactation. This larger mAHP may be necessary to limit the explosive bursts during milk ejection.

Simultaneous exposure to ATP and phenylephrine induces a sustained elevation in the intracellular calcium concentration in supraoptic neurons

“…In this preparation, basal [Ca 2ϩ ] i was similar to that reported previously in isolated dispersed SON neurons (8) and in individual neurons in slice preparations containing SON (21,34). The occurrence of spontaneous fluctuations in [Ca 2ϩ ] i was also similar to that observed in isolated SON neurons (8).…”

“…Although previous studies have used live cell Ca 2ϩ imaging techniques to study the effect of glutamate, ATP, and neuropeptides on cytoplasmic [Ca 2ϩ ] i in SON neurons (8,13,15,18,(22)(23)(24), to identify the types of Ca 2ϩ channels used (22), and to study the role of Ca 2ϩ in regulating the ionic currents in SON neurons (20,21,34), this is the first study to measure changes in [Ca 2ϩ ] i in response to ATP and an ␣1-adrenergic agonist in SON neurons maintained in an organotypic preparation. In this preparation, basal [Ca 2ϩ ] i was similar to that reported previously in isolated dispersed SON neurons (8) and in individual neurons in slice preparations containing SON (21,34).…”

Two Slow Calcium-Activated Afterhyperpolarization Currents Control Burst Firing Dynamics in Gonadotropin-Releasing Hormone Neurons

“…We show here that a critical feature for burst firing by GnRH neurons is their ability to exhibit prolonged Ca 2ϩ transients that act, in turn, to control very slow I AHP s that regulate intraburst and interburst properties. It is interesting to note that magnocellular oxytocin and vasopressin neurons can exhibit somewhat similar bursting behaviors to GnRH neurons but do not exhibit prolonged calcium transients or use calcium-dependent potassium channels in the same manner (Li and Hatton, 1997;Ghamari-Langroudi and Bourque, 2004;Teruyama and Armstrong, 2005). The dynamics of Ca 2ϩ transients in GnRH neurons are unique in the mature nervous system as is the existence of a very slow AHP generated by two sI AHP s in these cells.…”

Enhanced NMDA receptor-mediated intracellular calcium signaling in magnocellular neurosecretory neurons in heart failure rats

“…Both types of Ca 2ϩ -sensitive channels are expressed in MNCs and play important though opposing roles in regulating membrane excitability and firing properties in these neurons. Thus, whereas SK channels mediate an afterhyperpolarization (AHP) that acts to inhibit repetitive firing (21,59,64), CAN channels promote firing activity, in part via generation of fast depolarizing after potentials (fDAPs) (16,63,65). Importantly, both AHPs and DAPs temporally overlap, being their balance then a critical factor that determines the influence of ⌬Ca 2ϩ on membrane excitability (1).…”