Login / Signup

Phosphatidylinositol 4,5-bisphosphate (PIP2 ) modulates afterhyperpolarizations in oxytocin neurons of the supraoptic nucleus.

Matthew K KirchnerRobert C FoehringLie WangGiri Kumar ChandakaJoseph C CallawayWilliam E Armstrong
Published in: The Journal of physiology (2017)
Oxytocin (OT)- and vasopressin (VP)-secreting magnocellular neurons of the supraoptic nucleus (SON) display calcium-dependent afterhyperpolarizations (AHPs) following a train of action potentials that are critical to shaping the firing patterns of these cells. Previous work demonstrated that the lipid phosphatidylinositol 4,5-bisphosphate (PIP2 ) enabled the slow AHP component (sAHP) in cortical pyramidal neurons. We investigated whether this phenomenon occurred in OT and VP neurons of the SON. Using whole cell recordings in coronal hypothalamic slices from adult female rats, we demonstrated that inhibition of PIP2 synthesis with wortmannin robustly blocked both the medium and slow AHP currents (ImAHP and IsAHP ) of OT, but not VP neurons with high affinity. We further tested this by introducing a water-soluble PIP2 analogue (diC8 -PIP2 ) into neurons, which in OT neurons not only prevented wortmannin's inhibitory effect, but slowed rundown of the ImAHP and IsAHP . Inhibition of phospholipase C (PLC) with U73122 did not inhibit either ImAHP or IsAHP in OT neurons, consistent with wortmannin's effects not being due to reducing diacylglycerol (DAG) or IP3 availability, i.e. PIP2 modulation of AHPs is not likely to involve downstream Ca2+ release from inositol 1,4,5-trisphosphate (IP3 )-triggered Ca2+ -store release, or channel modulation via DAG and protein kinase C (PKC). We found that wortmannin reduced [Ca2+ ]i increase induced by spike trains in OT neurons, but had no effect on AHPs evoked by uncaging intracellular Ca2+ . Finally, wortmannin selectively reduced whole cell Ca2+ currents in OT neurons while leaving VP neurons unaffected. The results indicate that PIP2 modulates both the ImAHP and IsAHP in OT neurons, most likely by controlling Ca2+ entry through voltage-gated Ca2+ channels opened during spike trains.
Keyphrases
  • spinal cord
  • protein kinase
  • water soluble
  • stem cells
  • spinal cord injury
  • single cell
  • young adults
  • cell therapy
  • bone marrow
  • induced apoptosis
  • high speed
  • signaling pathway
  • high resolution
  • disease virus