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

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 (I_mAHP). In slices from virgin and two groups of pregnant rats [embryonic days (E18-19, or E20-21], I_mAHPs were evoked with 3-, 10-, and 17-spike trains (20 Hz). With 3-spike trains, TBB increased the I_mAHP 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 I_mAHPs were similar among groups with 17-spike trains. In contrast, OA, while consistently reducing the I_mAHP 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 I_mAHP, contributing to the enhanced I_mAHP. 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.