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

Postinfarction Changes in Cardiac Na+ Channel. Introduction: After a myocar dial infarction (MI), the heart undergoes a remodeling process that include s 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 arrhythmogenici ty 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 ventricula r myocardium. Methods and Results: Using a macropatch technique, we showed increased Nachannel bursting activity during sustained depolarization in post-MI remode led myocytes resulting in a large slow component of the I-Na decay, A tetro dotoxin-sensitive current contributed 18% to the prolonged APD(90) of isola ted post-MI myocytes compared with 6% in control myocytes. Our molecular st udies revealed that, in addition to the rat heart I (rH I) subtype, thought to be the predominant subtype that encodes a tetrodotoxin-resistant isofor m, the brain subtypes NaCh I and NaCh Ia also are expressed in the rat myoc ytes, Post-MI remodeled myocardium showed increased expression of NaCh I pr otein with reversion of the NaCh Ia/NaCh I isoform ratio toward the fetal p henotype. Conclusion: Our findings raise the possibility that the increase in the slo w component of I-Na in post-MI remodeled myocytes is secondary to the incre ased expression of NaCh I. Additional studies are required to address these questions and to characterize the functional role of the NaCh I subtypes i n cardiac myocytes.