Kir4.1 is specifically expressed and active in non‐myelinating Schwann cells

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.

Characterisation of GFAP-Expressing Glial Cells in the Dorsal Root Ganglion after Spared Nerve Injury

“…These electrophysiology findings are congruent with transcriptomic data of adult nmSCs, demonstrating the expression of K v 1.1, K v 1.2 and K v 1.6, but not K ir 4.1 [8,20]. Interestingly, in embryonic and post-natal development, nmSCs of the nerve have K ir 4.1 currents [45,46]. Perhaps, K ir 4.1 currents become reduced in nmSCs, while they are maintained in SGCs in adulthood during development and maturation.…”

Decoding muscle-resident Schwann cell dynamics during neuromuscular junction remodeling

“…Our unbiased clustering approach using uniform manifold approximation and projection (UMAP) classified 4d), while tSC clusters presented the expression of recently reported non-myelin SC markers, Ng2 and Kir4.1 (Fig. 4d) 31,33 . Additionally, tSC clusters prominently expressed the essential NMJ organizing gene, Agrn 34 , the neurotrophic receptor gene, nerve growth factor receptor (Ngfr), and cyclin-D1 (Ccnd1) a recognized gene associated with Schwann cell proliferation (Fig.…”

Progress in methods for evaluating Schwann cell myelination and axonal growth in peripheral nerve regeneration via scaffolds

“…Generally, SCs are divided into myelinating and non-myelinating cell types. Myelinating SCs ensheath axons to facilitate the conduction of electric impulses during nervous activity, while non-myelinating SCs, such as Remak SCs, surround axons of small caliber and provide trophic support to unmyelinated axons (Brifault et al, 2020;Bosch-Queralt et al, 2023;Procacci et al, 2023). In addition to forming myelin sheaths around axons and secreting neurotrophic factors, SCs can also regulate sensory perception and facilitate cell communications between synapses (Faroni et al, 2014).…”