Atrial GIRK channels mediate the effects of vagus nerve stimulation on heart rate dynamics and arrhythmogenesis

Steven W. Lee, Allison Anderson, Pilar A. Guzman, Atsushi Nakano, Alena Talkachova, Kevin D Wickman

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Diminished parasympathetic influence is central to the pathogenesis of cardiovascular diseases, including heart failure and hypertension. Stimulation of the vagus nerve has shown promise in treating cardiovascular disease, prompting renewed interest in understanding the signaling pathway(s) that mediate the vagal influence on cardiac physiology. Here, we evaluated the contribution of G protein-gated inwardly rectifying K+ (GIRK/Kir3) channels to the effect of vagus nerve stimulation (VNS) on heart rate (HR), HR variability (HRV), and arrhythmogenesis in anesthetized mice. As parasympathetic fibers innervate both atria and ventricle, and GIRK channels contribute to the cholinergic impact on atrial and ventricular myocytes, we collected in vivo electrocardiogram recordings from mice lacking either atrial or ventricular GIRK channels, during VNS. VNS decreased HR and increased HRV in control mice, in a muscarinic receptor-dependent manner. This effect was preserved in mice lacking ventricular GIRK channels, but was nearly completely absent in mice lacking GIRK channels in the atria. In addition, atrial-specific ablation of GIRK channels conferred resistance to arrhythmic episodes induced by VNS. These data indicate that atrial GIRK channels are the primary mediators of the impact of VNS on HR, HRV, and arrhythmogenesis in the anesthetized mouse.

Original languageEnglish (US)
Article number943
JournalFrontiers in Physiology
Volume9
Issue numberJUL
DOIs
StatePublished - Jul 19 2018

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Vagus Nerve Stimulation
Heart Rate
Cardiovascular Diseases
Muscarinic Receptors
GTP-Binding Proteins
Muscle Cells
Cholinergic Agents
Electrocardiography
Heart Failure
Hypertension

Keywords

  • Arrhythmogenesis
  • Atrial
  • GIRK channel
  • Kir3
  • Parasympathetic
  • Vagus nerve stimulation

PubMed: MeSH publication types

  • Journal Article

Cite this

Atrial GIRK channels mediate the effects of vagus nerve stimulation on heart rate dynamics and arrhythmogenesis. / Lee, Steven W.; Anderson, Allison; Guzman, Pilar A.; Nakano, Atsushi; Talkachova, Alena; Wickman, Kevin D.

In: Frontiers in Physiology, Vol. 9, No. JUL, 943, 19.07.2018.

Research output: Contribution to journalArticle

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