Abstract 16625: Neuronal Sodium Channels Contribute Significantly to Cardiac Repolarization During Ischemia
Introduction: It has been demonstrated that neuronal sodium channels (nNavs) are overexpressed around infracted areas and during ischemia. The role of nNavs expression during cardiac ischemia is still unknown. Based on the fact that ischemia depolarizes the membrane potential and that nNavs activate and remain more available at depolarized potentials than the cardiac sodium channels (Nav1.5), we hypothesised that overexpression of nNavs channels acts as a safety margin to preserve cardiac conduction. However, nNavs have a larger late current (INaL) than Nav1.5 and their expression may prolong the action potential duration (APD) thus creating an arrythmogenic substrate (AS). To test these hypotheses we measured the contribution of the nNavs to INa and INaL in ischemic condition in dog heart.
Methods: Freshly isolated dog cardiomyocytes were placed under ischemic conditions for 45 minutes. INaL and INa were recorded using the patch clamp technique in whole cell configuration. Tetrodotoxin (a specific nNavs blocker) and MTSEA (a specific Nav1.5 blocker) were used to differentiate the two sodium channels isoforms.
Results: In normal condition, INaL represents 0.3% of the peak current at a potential of -10 mV. Contribution of nNavs (TTX sensitive) to INaL was 36% ± 5%. The nNavs accounted for 11% of peak current. Ischemia decreased maximal peak current density from -73.3 nA/pF to -53.4 nA/pF. Surprisingly, nNavs contribution to peak INa was not modified. Ischemia however increased INaL from 0.3% to 1.6% of peak current.
Conclusion: The increased contribution of nNavs to INaL during ischemia can play a critical role in APD and facilitate the triggering of ischemia-related arrhythmias. This is the first report of a potential contribution of nNavs to ventricular repolarization. The results may have important implications for epilepsy and ischemia-related arrhythmias.
- © 2011 by American Heart Association, Inc.