Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Chronic Kidney Disease–Associated Pruritus is Caused by Dysregulated Ion Channels in Sensory Neurons

Akishi Momose
* ORCID logo ,
Michihiko Yabe
,
Shigetoshi Chiba
,
Kenjirou Kumakawa
,
Yasuo Shiraiwa
,
Hiroki Mizukami
Version 1 : Received: 13 September 2019 / Approved: 14 September 2019 / Online: 14 September 2019 (19:00:34 CEST)

A peer-reviewed article of this Preprint also exists.

Momose, A.; Yabe, M.; Chiba, S.; Kumakawa, K.; Shiraiwa, Y.; Mizukami, H. Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus. Medicines 2019, 6, 110. Momose, A.; Yabe, M.; Chiba, S.; Kumakawa, K.; Shiraiwa, Y.; Mizukami, H. Role of Dysregulated Ion Channels in Sensory Neurons in Chronic Kidney Disease-Associated Pruritus. Medicines 2019, 6, 110.

Abstract

Background: We investigated ion channels at the skin, including peripheral nerve endings, which serve as output machines and molecular integrators of many pruritic inputs mainly received by multiple G protein-coupled receptors (GPCRs). Methods: Based on the level of chronic kidney disease–associated pruritus (CKD-aP), subjects were divided into two groups: non-CKD-aP (no or slight pruritus; n=12) and CKD-aP (mild, moderate, or severe pruritus; n=11). Skin samples were obtained from the forearm or elbow during operations on arteriovenous fistulas. We measured ion channels expressed at the skin, including peripheral nerve endings by RT-PCR: Nav1.8, Kv1.4, Cav2.2, Cav3.2, BKCa, Anoctamin1, TRPV1, TRPA1, and ASIC. Results: Expression of Cav3.2, BKCa, and anoctamin1 was significantly elevated in patients with CKD-aP. On the other hand, expression of TRPV1 was significantly reduced in these patients. We observed no significant difference in the levels of Cav2.2 or ASIC between subjects with and without CKD-aP. TRPA1, Nav1.8，and Kv1.4 were not expressed. Conclusions: It was concluded that this greater difference in expression of ion channels at the skin tissue including specific for cutaneous peripheral nerve endings in CKD patients with CKD-aP may increase generator potential related to itching.

Keywords

uremic pruritus; ion channels; cell signaling; Cav3.2 calcium channel; RT-PCR; skin

Subject

Medicine and Pharmacology, Urology and Nephrology

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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