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221 Altered biophysical properties of the voltage-gated sodium channels in mouse atrial and ventricular cardiomyocytes
  1. Sian-Marie O’Brien,
  2. Andrew Holmes,
  3. Geroge Parnell,
  4. Clara Apicella,
  5. Larissa Fabritz,
  6. Paulus Kirchhof,
  7. Davor Pavlovic
  1. The University of Birmingham

Abstract

Introduction Several antiarrhythmic drugs target the cardiac sodium current INA. There is an increasing interest in atrial-specific ion channel inhibition, e.g. to allow selective antiarrhythmic drug development for the treatment of atrial fibrillation. Here, we sought to compare voltage-gated sodium currents (INA) in atrial and ventricular cardiomyocytes in mice, as Na+ channel subunits have been found to differ between atria and ventricles in rat and man.

Aim The aim of this study is to examine whether biophysical properties of INA are altered in mouse atrial cardiomyocytes compared to left ventricular cardiomyocytes.

Methods Na+ channel currents were measured using whole-cell voltage clamp in left atrial and left ventricular cardiomyocytes. Expression of Nav1.5 proteins and their regulatory ?-subunits was measured by western blotting in left atrial, right atrial and left ventricular tissue of wild-type 129/sv mice (15-20 weeks). Protein levels were normalised against calnexin.

Results Mean peak INA was significantly increased in left atrial myocytes compared to left ventricular (LA=−28.631.856pA/pF; n=15/4 cells/mice; LV =-19.834.186pA/pF; n=5/2 cells/mice; *p<0.05) and V50 for INA inactivation was significantly more negative in left atrial compared to left ventricular myocytes (LA=−92.41.877mV; n=16/4 cells/mice; LV=−81.772.413mV; n=5/2 cells/mice; *p<0.01). No difference in Nav1.5 expression was detected between chambers, however, expression of Ã?Â22 and Ã?Â24 subunits was significantly reduced in atrial tissue compared to left ventricular (LA=0.1890.02014; RA=0.30230.0333; LV=0.7360.0718; *p<0.01; n=4) and (LA=0.001450.00033; RA=0.002040.00102; LV=0.02140.000613; *p<0.01; n=4) respectively.

Conclusion Mouse atrial cardiomyocytes display increased INA compared to cardiomyocytes isolated from the ventricles. Alterations in biophysical properties of INA in mouse atrial myocytes may be attributable to reduced expression of the Nav1.5 Ã?Â22 and Nav1.5 Ã?Â24 subunits. Considering the interaction between Nav1.5 and its Ã?Â2 subunits may provide novel targets for antiarrhythmic drug therapy.

  • ATRIAL
  • SODIUM
  • CARDIOMYOCYTE

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