Spatial alterations of Kv channels expression and K+ currents in post-MI remodeled rat heart

Objective: The hypothesis being tested in the present study is that increased anisotropic properties occurs in the remodeled post-infarction heart due to spatial alterations in Kv channels expression and K+ currents of the remodeled myocardium. Methods: Three to 4 weeks post myocardial infarction (MI) in the rat, we measured the two components of the outward K+ current, I</it><inf>to-fast (f)</inf> and I</it><inf>to-slow(s)</inf> in the epicardium (epi) and endocardium (endo) of noninfarcted remodeled left ventricle (LV) using patch clamp techniques. Alterations in mRNA and/or protein levels of potassium channel genes Kv1.4, Kv1.5, Kv2.1, Kv4.2 and Kv4.3 were measured in epi, midmyocardium (mid), and endo regions of LV and in the right ventricle (RV). Results: In sham operated rat heart, the density of I</it><inf>to-f</inf> was 2.3 times greater in epi compared to endo myocytes. In post-MI heart, the density of I</it><inf>to-f</inf> and I</it><inf>to-s</inf> decreased to a similar degree in LV epi and endo but the difference in I</it><inf>to-f</inf> density between epi and endo persisted. The mRNA and/or protein levels of Kv1.4, Kv2.1, Kv4.2 and Kv4.3 but not Kv1.5 decreased to a varying extent in different regions of LV but not in RV of post-MI heart. Conclusions: Our results suggest that regional downregulation of Kv channels expression and density of K+ currents can be a significant determinant of increased spatial electrophysiological heterogeneity and contribute to increased electrical instability of the post-MI heart.