Molecular Insights into the Possible Role of Kir4.1 and Kir5.1 in Thyroid Hormone Biosynthesis

Abstract

Introduction: Thyroid morphogenesis is a complex process. Inwardly rectifying potassium (Kir) genes play a role in hormone release, cell excitability, pH and K⁺ homeostasis in many tissues. Objectives: To investigate the thyroid developmental expression of three members, Kir4.1, Kir4.2 and Kir5.1, in mice. To postulate the K⁺ channel role in thyroid hormone secretion. Material and Methods: Quantitative RT-PCR analysis of Kir4.1, Kir4.2 and Kir5.1 in mice of different stages (E13.5-E18.5). Results: mRNA for Kir4.1, Kir4.2 and Kir5.1 were identified and increased with age in mice. Both Kir4.1 and Kir4.2 genes are better expressed after E16.5. Kir4.2 greatly increases from E13.5 to E16.5 (p ≤ 0.05). Conclusion: Quantitative PCR shows that the mouse thyroid presents increased expression for Kir channels during development. The role of Kir in thyroid morphogenesis and differentiation might be understood in future studies. We speculate that thyroglobulin trafficking might be modulated by Kir4.1/5.1.

Melatonin protects Kir2.1 function in an oxidative stress‐related model of aging neuroglia

“…Inwardly rectifying K + (Kir) channels belong to a large family of potassium channels which comprises seven subfamilies (Kir1.x–Kir7.x) that are abundantly expressed and show distinctive features in many different tissues and cell types, such as kidney epithelial cells (Kir1.1/KCNJ1, or renal outer medullary potassium channel ROMK1 52 ); cardiac myocytes (Kir2.x, Kir3.x, and Kir6.x channels 53 ); brain cortical neurons and glia cells (various members of the Kir2, Kir3, Kir4, and Kir6 subfamilies 54 ); thyroid epithelial cells (Kir 5.1/KCNJ16 55 ); and pancreatic β cells (Kir6.1/KCNJ8 and Kir6.2/KCNJ11 56 ). Due to the intrinsic properties of the open‐channel pore as well as an asymmetric open‐channel pore block by intracellular divalent cations and polyamines, Kir channels facilitate a greater influx of potassium ions rather than an efflux—the so‐called inward rectification.…”

Targeting the inward rectifier potassium channel 5.1 in thyroid cancer: artificial intelligence-facilitated molecular docking for drug discovery

“…However, this hypothesis requires further investigation. The Kir4.1, Kir4.2, Kir5.1 mRNA levels had significantly increased during mouse thyroid gland development [13]. Targeting Kir5.1 may be a promising strategy for patients with an RAIR status.…”

“…Kir5.1 (encoded by KCNJ16) is the only identified member of the Kir5.x subfamily. Kir5.1 mRNA has been identified in several important organs, such as the brain, thyroid, parathyroid gland, kidney, liver, testis, and adrenal glands as a K+ transport channel [10][11][12][13]. Generally, a functional Kir channel is a tetrameric complex that can be either homomeric or heteromeric.…”

Diverse functions of the inward-rectifying potassium channel Kir5.1 and its relationship with human diseases

“…At present, studies on Kir5.1 and cancer mainly focus on the thyroid, pancreas, and prostate, among others, and the expression changes of Kir5.1 are not consistent in different glands during carcinogenesis (Table 1). In 2014, Ramos et al found that Kir5.1, Kir4.1, and Kir4.2 were significantly expressed in the thyroid, but the function of Kir5.1 in the thyroid was unclear, although it was suggested to be involved in the transport of thyroglobulin (Ramos et al, 2015). Liu et al analyzed mRNA datasets from 23 anaplastic thyroid cancer (ATC) samples and 24 normal samples and identified 55 differentially expressed genes (DEGs).…”