Regional gradation of L-type calcium currents in the feline heart with a healed myocardial infarct

Introduction: Abnormal action potentials in myocytes adjacent to > 2- month-old feline LV myocardial infarcts (MI) may reflect alterations in Ca²⁺ currents (I(ca)). Methods and Results: We compared I(Ca), at 36°C, in subendocardial myocytes isolated from areas adjacent to MI and to I(Ca) in cells from remote areas (> 4 mm away; REM) and control cells from similar regions in normal hearts. Control (CON) myocytes had membrane capacitance of 234 ± 10 pF (n = 81 cells) compared to 305 ± 14 pF in REM (71 cells; P < 0.05 from CON) and 237 ± 11 pF (n = 55 cells) in MI (not different from CON). From V(h) = -40 mV, peak I(Ca) elicited by test potentials (-35 to +70 mV) were significantly larger in CON (-1746 ± 123 pA) and REM (-1795 ± 142 pA) compared to MI (-1352 ± 129 pA) (P < 0.05). Peak I(Ca) density was significantly reduced in REM (-6.0 ± 0.4 pA/pF) or MI (-5.7 ± 0.4 pA/pF, P < 0.05) compared to CON (-7.5 ± 0.4 pA/pF). Double exponential I(Ca) decay was similar among groups. Half-inactivation potential (V_0.5) was significantly shifted (hyperpolarizing direction) for MI (-29.1 ± 2.6 mV) and REM (-24.6 ± 1.2 mV) myocytes compared to -20.3 ± 1.0 mV in CON.MI slope factor (k; 9.0 ± 0.5) was significantly different from CON (6.8 ± 0.3) and REM (7.3 ± 0.4). No differences in time course of recovery from inactivation were noted. Five millimolar Ba²⁺(o) produced significant increases in I(Ca) in CON and REM but an attenuated response in MI. Bay K8644 (1 μM) produced similar I(Ca) increase in all groups. I(Ca) increase due to isoproterenol (1 μM) in MI and REM was half that in CON, but there were no differences in increased I(Ca) responses among groups following phenylephrine (10 μM). Conclusion: Reduced I(Ca) density in REM reflects cell hypertrophy, whereas altered I(Ca) of MI may reflect altered channel structure and/or function.