Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig

It was previously demonstrated that transmural electrophysiological heterogeneities can inscribe the ECG T wave. However. the bifurcated T wave Caused by loss of inward rectifier potassium current (I-K1) function is not fully explained by transmural heterogeneities. Since right ventricullar (RV) guinea pig myocytes have significantly lower I-K1 than left ventricullar (LV) myocytes. we hypothesized that the complex ECG can be inscribed by heterogeneous chamber-specific responses to hypokalemia and partial IK, blockade. Ratiometric optical action potentials were recorded from the epicardial Surface of the RV and LV. BaCl (10 mu mol/l) was perfused to partially block I-K1 I in isolated guinea pig whole heart preparations. BaCl2 or hypokalemia alone sinilificantly increased RV basal (RVB) action potential duration (APD) by similar to 30% above control compared with LV apical (LVA) APD (14%, P < 0.05). In the presence of BaCl, 2 mmol/l extracellular potassium (hypoka lemia) further increased RVB APD to a greater extent (31 %) than LV, APD (19%. P < 0.05) compared with BaCl, perfusion alone. Maximal dispersion between RVB and LVA APD increased by 105% (P < 0.05). and the QT interval prolonged by 55% (P < 0.05) during hypokalemia and BaCl2. Hypokalemia and BaCl, produced an ECG With I double repolarization wave. The first wave (QT I) corresponded to selective depression of apical LV plateau potentials, while the second wave (QT2) corresponded to the latest repolarizing RVB myocytes, These data Suggest that final repolarization is more sensitive to extracellular potassium changes in regions with reduced I-K1, particularly when I-K1, availability is reduced. Furthermore, Underlying I-K1 heterogeneities can potentially contribute to the complex ECG during I-K1 loss of function and hypokalemia.