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

Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, Salt Lake City, Utah

Submitted 30 November 2006 ; accepted in final form 12 February 2007

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 ventricular (RV) guinea pig myocytes have significantly lower I_K1 than left ventricular (LV) myocytes, we hypothesized that the complex ECG can be inscribed by heterogeneous chamber-specific responses to hypokalemia and partial I_K1 blockade. Ratiometric optical action potentials were recorded from the epicardial surface of the RV and LV. BaCl₂ (10 µmol/l) was perfused to partially block I_K1 in isolated guinea pig whole heart preparations. BaCl₂ or hypokalemia alone significantly increased RV basal (RV_B) action potential duration (APD) by 30% above control compared with LV apical (LV_A) APD (14%, P < 0.05). In the presence of BaCl₂, 2 mmol/l extracellular potassium (hypokalemia) further increased RV_B APD to a greater extent (31%) than LV_A APD (19%, P < 0.05) compared with BaCl₂ perfusion alone. Maximal dispersion between RV_B and LV_A APD increased by 105% (P < 0.05), and the QT interval prolonged by 55% (P < 0.05) during hypokalemia and BaCl₂. Hypokalemia and BaCl₂ produced an ECG with a double repolarization wave. The first wave (QT1) corresponded to selective depression of apical LV plateau potentials, while the second wave (QT2) corresponded to the latest repolarizing RV_B 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.

electrophysiology; waves; electrocardiography; interventricular heterogeneities; inward rectifier potassium current

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