Kir4.1 is specifically expressed and active in non‐myelinating Schwann cells. Issue 4 (8th December 2022)

• Record Type: Journal Article
• Authors: Procacci, Nicole M.; Hastings, Robert Louis; Aziz, Aamir A.; Christiansen, Nina M.; Zhao, Jie; DeAngeli, Claire; LeBlanc, Normand; Notterpek, Lucia; Valdez, Gregorio; Gould, Thomas W.
• Is Part Of: Glia. Volume 71:Issue 4(2023)
• Page Start: 926
• Page End: 944
• Publication Date: 2022-12-08
• Subjects: glia -- Kir4.1 -- myelination -- neuromuscular junction -- Schwann cells -- synapse; Neuroglia -- Periodicals; Neurology -- Periodicals; 611.0188
• DOI: 10.1002/glia.24315
• Languages: English
• ISSNs: 0894-1491

Abstract

Abstract: Non‐myelinating Schwann cells (NMSC) play important roles in peripheral nervous system formation and function. However, the molecular identity of these cells remains poorly defined. We provide evidence that Kir4.1, an inward‐rectifying K+ channel encoded by the KCNJ10 gene, is specifically expressed and active in NMSC. Immunostaining revealed that Kir4.1 is present in terminal/perisynaptic SCs (TPSC), synaptic glia at neuromuscular junctions (NMJ), but not in myelinating SCs (MSC) of adult mice. To further examine the expression pattern of Kir4.1, we generated BAC transgenic Kir4.1‐CreER T2 mice and crossed them to the tdTomato reporter line. Activation of CreER T2 with tamoxifen after the completion of myelination onset led to robust expression of tdTomato in NMSC, including Remak Schwann cells (RSC) along peripheral nerves and TPSC, but not in MSC. In contrast, activating CreER T2 before and during the onset of myelination led to tdTomato expression in NMSC and MSC. These observations suggest that immature SC express Kir4.1, and its expression is then downregulated selectively in myelin‐forming SC. In support, we found that while activating CreER T2 induces tdTomato expression in immature SC, it fails to induce tdTomato in MSC associated with sensory axons in culture. NMSC derived from neonatal sciatic nerve were shown to express Kir4.1 and exhibit barium‐sensitive inwardly rectifying macroscopic K + currents. Thus, this study identified Kir4.1 as a potential modulator of immature SC and NMSC function. Additionally, it established a novel transgenic mouse line to introduce or delete genes in NMSC. Main Points: Kir4.1‐CreER T2 mice were developed to track Kir4.1 expression. Using this genetic tool, we observed that Kir4.1 is initially expressed in immature Schwann cells, downregulated in myelinating Schwann cells and maintained in non‐myelinating Schwann cells of peripheral nerves and at the NMJ.