The expression of ion channels in sensory neurons that can shift action potential in direction to hyperpolarization are dysregulated in patients with chronic kidney disease–associated pruritus

Abstract

Background: Expression levels of voltage-dependent T-type calcium channel subunit alfa 1H (Cav3.2), big conductance calcium-activated potassium channel (BKCa), and anoctamin 1 in the skin, including in peripheral nerve endings were previously found to be significantly elevated in patients with chronic kidney disease (CKD)–associated pruritus (CKD-aP). On the other hand, the expression of transient receptor potential 1 was significantly reduced. Methods: We further compared CKD patients with and without CKD-aP in terms of the expression levels of several ion channels 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 reverse transcriptional polymerase chain reaction (RT-PCR)to measure the skin expression levels of the following ion channels in the skin: voltage gated sodium channel 1.7 (Nav1.7), voltage gated potassium channel 7.2 (Kv7.2), TWIK-related K+ channel 1 (TREK1), hyperpolarization-activated cyclic nucleotide-gated channel type 2 (HCN2), tyrosine kinase receptor A (TrkA), and piezo-type mechano-sensitive ion channel component 2 (Piezo2). Results: 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. Conclusion: In skin samples collected from CKD-aP patients, ion channel expression patterns were altered to enhance hyperpolarization of pruriceptive neurons.