Basic & Clinical Medicine ›› 2020, Vol. 40 ›› Issue (1): 73-77.

• Original Articles • Previous Articles     Next Articles

Pantoprazole induces bradyarrhythmia in mice with hypokalemia

LI Shuai1, ZHU Wen-gen1, YAN Xia2, LAI Wei1, YU Jian-hua1, WAN Rong2, HONG Kui1,2,3*   

  1. 1. Department of Cardiovascular Medicine;
    2. Jiangxi Provincial Key Laboratory of Molecular Medicine;
    3. Department of Medical Genetics, the Second Affiliated Hospital of Nanchang University, Nanchang 330006, China
  • Received:2019-01-21 Revised:2019-06-04 Online:2020-01-05 Published:2019-12-27
  • Contact: *hongkui88@163.com

Abstract: Objective To investigate the mechanism of arrhythmia induced by pantoprazole (PPZ) in mice with hypokalemia. Methods Mice were randomly divided into control group, PPZ group [20 mg/(kg·d), intraperitoneal injection for 5 weeks], furosemide (FS) group and FS+PPZ group. After 5 weeks, the ECG parameters (heart rate, PR interval, QRS interval, QTc interval) and spontaneous arrhythmia were monitored. The changes of the mRNA and protein expression of hyperpolarization-activated and cyclic nucleotide-cation channels 2 and 4 (HCN2 and HCN4), cardiac voltage-gated sodium channel alpha subunit (SCN5A), L-type calcium channel alpha subunit (CACNA1C) and T-type calcium channel alpha subunit (CACNA1G) were analysed by real-time fluorescence quantitative PCR and Western blot technology. Results Compared with control group, the HR was significantly decreased and PR interval was prolonged in PPZ group (P<0.01, P<0.05). Compared with FS group,the HR and PR interval in FS+PPZ group were further decreased and prolonged (P<0.01, P<0.05), and 4 mice developed sinus arrest (SA) (P<0.05). The expressions of HCN4 mRNA and protein in PPZ group were lower than those in control group (P<0.01), respectively, and the expression in FS+PPZ group was lower than those in FS group (P<0.01). The expression of HCN2 mRNA in PPZ group was lower than that in control group(P<0.05), which was further decreased in FS+PPZ group compared with FS group (P<0.01). Conclusions It is found that pantoprazole may lead to bradyarrhythmia in mice under hypokalemia, which may be related to abnormal expression of HCN2 and HCN4.

Key words: pantoprazole, hypokalemia, arrhythmia, mechanism

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