Alterations of sodium channel kinetics and gene expression in the postinfarction remodeled myocardium

After a myocardial infarction (MI), the heart undergoes a remodeling process that includes hypertrophy of noninfarcted left ventricular myocytes. Alterations in the genetic expression, including reexpression of fetal isogene patterns, can result in electrophysiologic changes that contribute to the arrhythmogenicity of post-MI heart. The present study investigated possible alterations in gene expression of Na+ channel subtypes, as well as the kinetics of the Na+ current (I(Na)), in 3- to 4-week-old post-MI rat remodeled left ventricular myocardium.

Using a macropatch technique, we showed increased Na+ channel bursting activity during sustained depolarization in post-MI remodeled myocytes resulting in a large slow component of the I(Na) decay. A tetrodotoxin-sensitive current contributed 18% to the prolonged APD90 of isolated post-MI myocytes compared with 6% in control myocytes. Our molecular studies revealed that, in addition to the rat heart I (rH I) subtype, thought to be the predominant subtype that encodes a tetrodotoxin-resistant isoform, the brain subtypes NaCh I and NaCh Ia also are expressed in the rat myocytes. Post-MI remodeled myocardium showed increased expression of NaCh I protein with reversion of the NaCh Ia/NaCh I isoform ratio toward the fetal phenotype.

Our findings raise the possibility that the increase in the slow component of I(Na) in post-MI remodeled myocytes is secondary to the increased expression of NaCh I. Additional studies are required to address these questions and to characterize the functional role of the NaCh I subtypes in cardiac myocytes.