Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Dysregulated Expression of Ion Channels in Sensory Neurons Enhances Action Potential Afterhyperpolarization in Patients with Chronic Kidney Disease–Associated Pruritus

Version 1 : Received: 29 July 2022 / Approved: 29 July 2022 / Online: 29 July 2022 (04:50:39 CEST)

How to cite: Momose, A.; Yabe, M.; Chiba, S.; Kumakawa, K.; Shiraiwa, Y.; Mizukami, H. Dysregulated Expression of Ion Channels in Sensory Neurons Enhances Action Potential Afterhyperpolarization in Patients with Chronic Kidney Disease–Associated Pruritus. Preprints 2022, 2022070449. https://doi.org/10.20944/preprints202207.0449.v1 Momose, A.; Yabe, M.; Chiba, S.; Kumakawa, K.; Shiraiwa, Y.; Mizukami, H. Dysregulated Expression of Ion Channels in Sensory Neurons Enhances Action Potential Afterhyperpolarization in Patients with Chronic Kidney Disease–Associated Pruritus. Preprints 2022, 2022070449. https://doi.org/10.20944/preprints202207.0449.v1

Abstract

Expression levels of Cav3.2, BKCa, and anoctamin 1 were previously found to be significantly elevated in patients with chronic kidney disease–associated pruritus (CKD-aP). On the other hand, the expression of TRPV1 was significantly reduced. We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels in the skin, including in peripheral nerve endings。Based on CKD-aP severity, subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n = 16) and CKD-aP (mild, moderate, or severe pruritus; n = 16). Skin samples were obtained from the forearm or elbow during arteriovenous fistula surgery. We used quantitative real-time polymerase chain reaction to measure the skin expression levels of the following ion channels in the skin: Nav1.7, Kv7.2, TREK1, HCN2, TrkA, and Piezo2. RT-PCR analyses showed that CKD-aP patients had significantly higher levels of TREK1 and Piezo2 transcripts and significantly lower levels of HCN2 transcripts than non–CKD-aP patients. No significant differences were noted between groups in the expression of Nav1.7 or TrkA. Moreover, Kv7.2 transcripts were not detected in either group. In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.

Keywords

CKD-aP; ion channels; action potential; hyperpolarization; RT-PCR

Subject

Medicine and Pharmacology, Dermatology

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