PIP2 alters of Ca2+ currents in acutely dissociated supraoptic oxytocin neurons

Matthew K. Kirchner, William E. Armstrong, Dongxu Guan, Yoichi Ueta, Robert C. Foehring

Research output: Contribution to journalArticle

Abstract

Magnocellular neurosecretory cells (MNCs) occupying the supraoptic nucleus (SON) contain voltage-gated Ca2+ channels that provide Ca2+ for triggering vesicle release, initiating signaling pathways, and activating channels, such as the potassium channels underlying the afterhyperpolarization (AHP). Phosphotidylinositol 4,5-bisphosphate (PIP2) is a phospholipid membrane component that has been previously shown to modulate Ca2+ channels, including in the SON in our previous work. In this study, we further investigated the ways in which PIP2 modulates these channels, and for the first time show how PIP2 modulates CaV channel currents in native membranes. Using whole cell patch clamp of genetically labeled dissociated neurons, we demonstrate that PIP2 depletion via wortmannin (0.5 μmol/L) inhibits Ca2+ channel currents in OT but not VP neurons. Additionally, it hyperpolarizes voltage-dependent activation of the channels by ~5 mV while leaving the slope of activation unchanged, properties unaffected in VP neurons. We also identified key differences in baseline currents between the cell types, wherein VP whole cell Ca2+ currents display more inactivation and shorter deactivation time constants. Wortmannin accelerates inactivation of Ca2+ channels in OT neurons, which we show to be mostly an effect on N-type Ca2+ channels. Finally, we demonstrate that wortmannin prevents prepulse-induced facilitation of peak Ca2+ channel currents. We conclude that PIP2 is a modulator that enhances current through N-type channels. This has implications for the afterhyperpolarization (AHP) of OT neurons, as previous work from our laboratory demonstrated the AHP is inhibited by wortmannin, and that its primary activation is from intracellular Ca2+ contributed by N-type channels.

Original languageEnglish (US)
Article numbere14198
JournalPhysiological Reports
Volume7
Issue number16
DOIs
StatePublished - Jan 1 2019

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Oxytocin
Neurons
Supraoptic Nucleus
Membranes
Potassium Channels
Phospholipids
wortmannin

All Science Journal Classification (ASJC) codes

  • Physiology
  • Physiology (medical)

Cite this

PIP2 alters of Ca2+ currents in acutely dissociated supraoptic oxytocin neurons. / Kirchner, Matthew K.; Armstrong, William E.; Guan, Dongxu; Ueta, Yoichi; Foehring, Robert C.

In: Physiological Reports, Vol. 7, No. 16, e14198, 01.01.2019.

Research output: Contribution to journalArticle

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