Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy

Lie Wang, Giri Kumar Chandaka, Robert Foehring, Joseph C. Callaway, William Armstrong

Research output: Contribution to journalArticle

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Abstract

Oxytocin (OT) neurons exhibit larger afterhyperpolarizations (AHPs) following spike trains during late pregnancy and lactation, times when these neurons fire in bursts and release more OT associated with labor and lactation. Calcium-dependent AHPs mediated by SK channels show this plasticity, and are reduced when the channel complex is phosphorylated by casein kinase 2 (CK2), and increased when dephosphorylated by protein phosphatase (PP)2A, by altering Ca2+ sensitivity. We compared AHP currents in supraoptic OT neurons after CK2 inhibition with 4,5,6,7-tetrabromobenzotriazole (TBB), or PP1-PP2A inhibition with okadaic acid (OA), to determine the roles of these enzymes in AHP plasticity, focusing on the peak current at 100 ms representing the SK-mediated, medium AHP (ImAHP). In slices from virgin and two groups of pregnant rats [embryonic days (E18–19, or E20–21], ImAHPs were evoked with 3-, 10-, and 17-spike trains (20 Hz). With 3-spike trains, TBB increased the ImAHP to the greatest extent in virgin compared with both groups of pregnant animals. A difference between virgins and E20–21 rats was also evident with a 10-spike train but the increases in ImAHPs were similar among groups with 17-spike trains. In contrast, OA, while consistently reducing the ImAHP in all cases, showed no differential effects among groups. In Western blots, CK2α, CK2β, PP2A-A, PP2A-B, and PP2A-C were found in supraoptic lysates, and expression of CK2α and CK2β was reduced in E20–21 rats. Coimmunoprecipitation revealed that calmodulin, CK2α, and PP2A-C were associated with SK3 protein. The results suggest that a downregulation of SK3-associated CK2α during late pregnancy may increase the sensitivity of the SK calmodulin (Ca2+) sensor for ImAHP, contributing to the enhanced ImAHP. NEW & NOTEWORTHY The article demonstrates for the first time that enhancement in spike afterhyperpolarizations in oxytocin neurons during pregnancy may be related to a downregulation in the smallconductance Ca2+-activated potassium channels (SK)/calmodulin binding protein casein kinase 2, which phosphorylates the SK channel complex and reduces its Ca2+ sensitivity.

Original languageEnglish (US)
Pages (from-to)1745-17252
Number of pages15508
JournalJournal of neurophysiology
Volume119
Issue number5
DOIs
StatePublished - May 1 2018

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Casein Kinase II
Potassium Channels
Oxytocin
Neurons
Pregnancy
Okadaic Acid
Lactation
Small-Conductance Calcium-Activated Potassium Channels
Down-Regulation
Calmodulin-Binding Proteins
Protein Phosphatase 2
Calcium-Calmodulin-Dependent Protein Kinases
Calmodulin
Protein Kinases
Western Blotting
Calcium

All Science Journal Classification (ASJC) codes

  • Neuroscience(all)
  • Physiology

Cite this

Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy. / Wang, Lie; Chandaka, Giri Kumar; Foehring, Robert; Callaway, Joseph C.; Armstrong, William.

In: Journal of neurophysiology, Vol. 119, No. 5, 01.05.2018, p. 1745-17252.

Research output: Contribution to journalArticle

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