β1-Adrenergic blocker bisoprolol reverses down-regulated ion channels in sinoatrial node of heart failure rats

Yuan Du, Junbo Zhang, Yutao Xi, Geru Wu, Ke Han, Xin Huang, Aiqun Ma, Tingzhong Wang

Research output: Contribution to journalArticlepeer-review

7 Scopus citations

Abstract

Bisoprolol, an antagonist of β1-adrenergic receptors, is effective in reducing the morbidity and mortality in patients with heart failure (HF). It has been found that HF is accompanied with dysfunction of the sinoatrial node (SAN). However, whether bisoprolol reverses the decreased SAN function in HF and how the relevant ion channels in SAN change were relatively less studied. SAN function and messenger RNA (mRNA) expression of sodium channels and hyperpolarization-activated cyclic nucleotide-gated (HCN) channel subunits were assessed in sham-operated rats, abdominal arterio-venous shunt (volume overload)-induced HF rats, and bisoprolol- treated HF rats. SAN cells of rats were isolated by laser capture microdissection. Quantitative real-time PCR analysis was used to quantify mRNA expression of sodium channels and HCN channel subunits in SAN. Intrinsic heart rate declined and sinus node recovery time prolonged in HF rats, indicating the suppressed SAN function, which could be improved by bisoprolol treatment. Nav1.1, Nav1.6, and HCN4 mRNA expressions were reduced in SAN in HF rats compared with that in control rats. Treatment with bisoprolol could reverse both the SAN function and the Nav1.1, Nav1.6, and HCN4 mRNA expression partially. These data indicated that bisoprolol is effective in HF treatment partially due to improved SAN function by reversing the down-regulation of sodium channels (Nav1.1 and Nav1.6) and HCN channel (HCN4) subunits in SAN in failing hearts.

Original languageEnglish (US)
Pages (from-to)293-302
Number of pages10
JournalJournal of Physiology and Biochemistry
Volume72
Issue number2
DOIs
StatePublished - Jun 1 2016
Externally publishedYes

Keywords

  • Bisoprolol
  • HCN channel
  • Heart failure
  • Remodeling
  • Sinoatrial node
  • Sodium channel

ASJC Scopus subject areas

  • Biochemistry
  • Physiology

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