Heart failure modulates electropharmacological characteristics of sinoatrial nodes

Shih Lin Chang, Hui Lun Chuang, Yao Chang Chen, Yu Hsun Kao, Yung Kuo Lin, Yung Hsin Yeh, Shih Ann Chen, Yi Jen Chen

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

The impact of heart failure (HF) on sinoatrial node (SAN) channel regulation and electropharmacological responses has remained elusive. The present study aimed to investigate the effects of HF on the electrical activity of SANs with and without pharmacological interventions. Action potentials (APs) were recorded in isolated SANs from normal rabbits (control) and those with HF (rapid ventricular pacing for 4 weeks) prior to and after administration of a funny current blocker (ivabradine; 0.1, 0.3, 3 or 10 μM), a calmodulin kinase II inhibitor (KN 93; 0.3 or 3 μM), a sarcoplasmic reticulum Ca2+ release inhibitor (ryanodine; 0.3 or 3 μM), a sodium current inhibitor (tetrodotoxin; 1, 3 or 10 μM) and a late sodium current inhibitor (ranolazine; 10 μM). Western blot analysis was used to investigate the protein expression in SANs from normal rabbits and those with HF. Control SANs had a higher beating rate than SANs from rabbits with HF (2.3±0.1 vs. 1.5±0.1 Hz; P<0.001). Similarly, ivabradine (10 μM), KN 93 (3 μM), ranolazine (10 μM) and ryanodine (3 μM) decreased the beating rates of SANs in the control (n=6) and HF (n=6) groups. Ivabradine treatment resulted in a higher incidence of AP block in HF vs. control SANs (66.7 vs. 0%; P<0.05). Tetrodotoxin (1, 3 or 10 μM) decreased the beating rate to a higher extent in SANs from rabbits with HF than in those from control rabbits and induced a higher incidence of AP block (66.7 vs. 0%; P<0.05). Furthermore, SANs from rabbits with HF had higher protein levels of phospholamban (PLB) and lower levels of hyperpolarization activated cyclic nucleotide gated potassium channel 4, ryanodine receptor and phosphorylated PLB than control SANs. In conclusion, HF modulates electropharmacological responses in the SAN by channel regulation, which may result in SAN dysfunction.

Original languageEnglish
Pages (from-to)771-779
Number of pages9
JournalExperimental and Therapeutic Medicine
Volume13
Issue number2
DOIs
Publication statusPublished - Feb 1 2017

Keywords

  • Heart failure
  • Ivabradine
  • KN-93
  • Ranolazine
  • Ryanodine
  • Tetrodotoxin

ASJC Scopus subject areas

  • Medicine(all)
  • Immunology and Microbiology (miscellaneous)
  • Cancer Research

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