Regional differences in the delayed rectifier current (IKr and IKs) contribute to the differences in action potential duration in basal left ventricular myocytes in guinea-pig

Objective: To compare the properties of single myocytes isolated from different layers of the basal region of the left ventricle and to test the hypothesis that differences in the delayed rectifier current (I-k) contribute to regional differences in action potential duration. Methods: Myocytes were isolated from basal sub-endocardial, mid-myocardial and sub-epicardial layers of the guinea-pig left ventricle. Membrane voltage and current were measured using the switch-clamp technique. Results: Mean action potential duration measured at 90% repolarisation (APD(90)) was longer in sub-endocardial myocytes than in mid-myocardial and sub-epicardial myocytes [APD(90) ms at 0.2 Hz: sub-endocardial 292 +/- 12 (n = 40), mid-myocardial 243 +/- 8 (n = 42) and sub-epicardial 227 +/- 9 (n = 36), P<0.001, analysis of variance (ANOVA)]. The APD-rate relationship (stimulation frequencies 2, 1, 0.2 and 0.017 Hz) was steeper in sub-endocardial than in mid-myocardial or sub-epicardial myocytes (P<0.001, ANOVA). The density of I-k was greater in mid-myocardial (4.05 +/- 0.09 pA pF(-1)) and sub-epicardial (3.90 +/- 0.41 pA pF(-1)) than in sub-endocardial myocytes (2.74 +/- 0.27 pA pF(-1), P<0.01 ANOVA). The rapidly activating (I-Kr) and slowly-activating (I-Ks) components of I-k were significantly smaller in sub-endocardial than in mid-myocardial or sub-epicardial myocytes. D,L-Sotalol-induced prolongation of APD(90) was similar in the three regions studied. Conclusions: There are significant transmural gradients in the electrophysiological properties of myocytes isolated from the base of the left ventricular free wall in guinea-pig. Sub-endocardial myocytes had a longer APD(90) attributable in part to a significantly smaller I-k density. We have been unable to identify M cells in the guinea-pig left ventricular free wall. (C) 1998 Elsevier Science B.V. All rights reserved.