Calcium channel heterogeneity in canine left ventricular myocytes

Abstract

Regional variations in the electrophysiological properties of myocytes across the left ventricular wall play an important role in both the normal physiology of the heart and the genesis of arrhythmias. To investigate the possible contributions of calcium channels to transmural electrical heterogeneity, whole-cell patch-clamp recordings were made from isolated canine epicardial and endocardial left ventricular myocytes. Two major differences in Ca2+ channel properties were found between epi- and endocardial cells. First, the L-type Ca2+ current was larger in endocardial than in epicardial myocytes. The average peak current density at +10 mV in endocardial myocytes was 3.4 ± 0.2 pA pF−1, and was 45 % higher than that in epicardium (2.3 ± 0.1 pA pF−1). The kinetic properties of the L-type current in epi- and endocardial cells were not significantly different. Second, a low-threshold, rapidly activating and inactivating Ca2+ current that resembled the T-type current was present in all endocardial myocytes but was small or absent in epicardial myocytes. This T-like current had an average peak density of 0.5 pA pF−1 at −40 mV in endocardial cells. In most endocardial cells the T-like Ca2+ current comprised two components: a Ni2+-sensitive T-type current and a tetrodotoxin-sensitive Ca2+ current. We conclude that there are considerable regional variations in the density and properties of Ca2+ channels across the canine left ventricular wall. These variations may contribute to the overall transmural electrical heterogeneity.