Changes in potassium channel modulation may underlie afterhyperpolarization plasticity in oxytocin neurons during late pregnancy
| Autor: | Lie Wang, Joseph C. Callaway, Robert C. Foehring, William E. Armstrong, Giri K Chandaka |
|---|---|
| Rok vydání: | 2018 |
| Předmět: |
0301 basic medicine
medicine.medical_specialty Vasopressin Patch-Clamp Techniques Small-Conductance Calcium-Activated Potassium Channels Vasopressins Physiology Action Potentials Down-Regulation Oxytocin Rats Sprague-Dawley 03 medical and health sciences 0302 clinical medicine Downregulation and upregulation Pregnancy Internal medicine medicine Animals Protein Phosphatase 2 Casein Kinase II Neurons Neuronal Plasticity Chemistry General Neuroscience Brain Afterhyperpolarization Protein phosphatase 2 medicine.disease Potassium channel Rats 030104 developmental biology Endocrinology Female Casein kinase 2 030217 neurology & neurosurgery Research Article medicine.drug |
| Zdroj: | Journal of Neurophysiology. 119:1745-1752 |
| ISSN: | 1522-1598 0022-3077 |
| DOI: | 10.1152/jn.00608.2017 |
| Popis: | 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 small-conductance Ca2+-activated potassium channels (SK)/calmodulin binding protein casein kinase 2, which phosphorylates the SK channel complex and reduces its Ca2+ sensitivity. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|