Regional differences in action potential characteristics and membrane currents of guinea-pig left ventricular myocytes

Regional differences in action potential characteristics and membrane currents were investigated in subendocardial, midmyocardial and subepicardial myocytes isolated from the left ventricular free wall of guinea-pig hearts. Action potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolarization (APD(90)) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocytes (n = 36). L-type calcium current (I-Ca) density and background potassium current (I-Kr) density were similar in the three regions studied. Delayed rectifier current (I-K) was measured as deactivating tail current, elicited on repolarization back to -45 mV after 2 s step depolarizations to test potentials ranging from -10 to +80 mV. Mean I-K density (after a step to +80 mV) was larger in subepicardial myocytes (1.59 +/- 0.16 pA pF(-1), n = 16) than in either subendocardial (1.16 +/- 0.12 pA pF(-1), n = 17) or midmyocardial (1.13 +/- 0.11 pA pF(-1), n = 21) myocytes (P < 0.05, ANOVA). The La3+-insensitive current (I-Ks) elicited on repolarization back to -45 mV after a 250 ms step depolarization to +60 mV was similar in the three regions studied. The La3+-sensitive tail current, (I-Kr) was greater in subepicardial (0.50 +/- 0.04 pA pF(-1), n = 11) than in subendocardial (0.25 +/- 0.05 pA pF(-1) n = 9) or in midmyocardial myocytes (0.38 +/- 0.05 pA pF(-1), n = 11, P < 0.05, ANOVA). The contribution of a Na+ background current to regional differences in APD was assessed by application of 0.1 mu M tetrodotoxin (TTX). TTX-induced shortening of APD(90) was greater in subendocardial myocytes (35.7 +/- 7.1 %, n = 11) than in midmyocardial (15.7 +/- 3.8 %, n = 10) and subepicardial (20.2 +/- 4.3 %, n = 11) myocytes (P < 0.05, ANOVA). Regional differences in action potential characteristics between subendocardial, midmyocardial, and subepicardial myocytes isolated from guinea-pig left ventricle are attributable, at least in part, to differences in I-K and Na+-dependent currents.