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

Regional differences in action potential characteristics and membrane curre nts were investigated in subendocardial, midmyocardial and subepicardial my ocytes isolated from the left ventricular free wall of guinea-pig hearts. A ction potential duration (APD) was dependent on the region of origin of the myocytes (P < 0.01, ANOVA). Mean action potential duration at 90 % repolar ization (APD(90)) was 237 +/- 8 ms in subendocardial (n = 30 myocytes), 251 +/- 7 ms in midmyocardial (n = 30) and 204 +/- 7 ms in subepicardial myocy tes (n = 36). L-type calcium current (I-Ca) density and background potassiu m current (I-Kr) density were similar in the three regions studied. Delayed rectifier current (I-K) was measured as deactivating tail current, elicite d on repolarization back to -45 mV after 2 s step depolarizations to test p otentials 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 midmyoc ardial (1.13 +/- 0.11 pA pF(-1), n = 21) myocytes (P < 0.05, ANOVA). The La 3+-insensitive current (I-Ks) elicited on repolarization back to -45 mV aft er 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 subepicardi al (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 regi onal differences in APD was assessed by application of 0.1 mu M tetrodotoxi n (TTX). TTX-induced shortening of APD(90) was greater in subendocardial my ocytes (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 subendocar dial, midmyocardial, and subepicardial myocytes isolated from guinea-pig le ft ventricle are attributable, at least in part, to differences in I-K and Na+-dependent currents.