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LKB1 deletion causes early changes in atrial channel expression and electrophysiology prior to atrial fibrillation

Grace E Kim1, Jenna L Ross2, Chaoqin Xie3

  • 1Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06520, USA.

Cardiovascular Research
|September 18, 2015
PubMed
Abstract

Insights

Liver kinase B1 (LKB1) deletion in mice causes early atrial electrical defects, impacting channel expression and conduction before fibrosis and atrial fibrillation (AF) develop. LKB1 is crucial for normal atrial development and function.

Area of Science:

  • Cardiovascular Biology
  • Molecular Cardiology
  • Electrophysiology

Background:

  • Liver kinase B1 (LKB1) is a key kinase activating AMP-activated protein kinase (AMPK).
  • LKB1 deficiency in mice results in cardiomyopathy and atrial fibrillation (AF).
  • The role of LKB1 in early atrial development and electrophysiology is not well understood.

Purpose of the Study:

  • To investigate the impact of cardiomyocyte-specific LKB1 deletion on atrial channel expression.
  • To determine the effects of LKB1 deletion on atrial electrophysiological function in a mouse model.
  • To elucidate the role of LKB1 in early atrial biology.

Main Methods:

  • Utilized a cardiomyocyte-specific LKB1 knockout mouse model (αMHC-Cre LKB1(fl/fl)).
  • Conducted gene expression analysis, histology, and echocardiography.
  • Performed in vitro patch-clamp, ex vivo optical mapping, and in vivo ECG recordings.

Main Results:

  • Early defects in atrial depolarization, Nav1.5, and Cx40 expression were observed in LKB1-deficient neonatal mice.
  • Reduced inward sodium current density in neonatal atrial myocytes.
  • Development of atrial fibrosis, AF, and impaired interatrial conduction by adulthood.

Conclusions:

  • LKB1 deletion leads to early atrial channel and electrophysiological defects.
  • These defects precede atrial remodeling, fibrosis, and AF onset.
  • LKB1 is essential for normal atrial growth and electrophysiological integrity.
Keywords:
Atrial fibrillationCellular signalling pathwaysLKB1

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