The Intermediate-conductance Calcium-activated Potassium Channel KCa3.1 Contributes to Alkalinization-induced Vascular Calcification in Vitro

Overview

Journal J Clin Lab Anal

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
Pathology

Date 2021 Jul 27

PMID 34313357

Citations 2

Authors

Yaling Bai

Jinsheng Xu

Shuo Yang

Huiran Zhang

Lei He

Wei Zhou

Meijuan Cheng

Shenglei Zhang

Affiliations

Soon will be listed here.

Abstract

Objective: In order to find new strategies for the prevention of vascular calcification in uremic individuals especially treated by dialysis and develop novel therapeutic targets in vascular calcification, we explore the role of KCa3.1 in alkalinization-induced VSMCs calcification in vitro.

Method: Rat VSMCs calcification model was established by beta-glycerophosphate (β-GP, 10 mM) induction. The pH of Dulbecco's modified Eagle's medium (DMEM) was adjusted every 24 h with 10 mM HCl or 10 mM NaHCO . The mineralization was measured by Alizarin Red staining and O-cresolphthalein complex one method. mRNA and protein expression were detected by RT-PCR and Western blot or immunofluorescence. Ca2+ influx was measured by Elisa.

Result: The results indicated that alkalization induced an increase in Ca2+ influx to enhance VSMCs calcification. Furthermore, the increase of calcification was associated with the expression of KCa3.1 via advanced expression of osteoblastic differentiation markers alkaline phosphatase (ALP) and Runt-related transcription factor 2 (Runx2). Blocking KCa3.1 with TRAM-34 or shRNA vector can significantly lowered the effects of calcification in the activity of ALP and Runx2 expression.

Conclusion: Together all, our studies suggested that alkalinization can promote vascular calcification by upregulating KCa3.1 channel and enhancing osteogenic/chondrogenic differentiation by upregulating Runx2. The specific inhibitor TRAM-34 and KCa3.1-shRNA ameliorated VSMCs calcification by downregulating KCa3.1.

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PMID: 39003292 PMC: 11246527. DOI: 10.1038/s41467-024-50317-w.

The intermediate-conductance calcium-activated potassium channel KCa3.1 contributes to alkalinization-induced vascular calcification in vitro.

Bai Y, Xu J, Yang S, Zhang H, He L, Zhou W J Clin Lab Anal. 2021; 35(8):e23854.

PMID: 34313357 PMC: 8373358. DOI: 10.1002/jcla.23854.

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