title: Heterogeneous ventricular chamber response to hypokalemia and inward rectifier potassium channel blockade underlies bifurcated T wave in guinea pig.
abstract: 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. BaCl(2) (10 micromol/l) was perfused to partially block I(K1) in isolated guinea pig whole heart preparations. BaCl(2) or hypokalemia alone significantly increased RV basal (RV(B)) action potential duration (APD) by approximately 30% above control compared with LV apical (LV(A)) APD (14%, P<0.05). In the presence of BaCl(2), 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 BaCl(2) 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 BaCl(2). Hypokalemia and BaCl(2) 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.
authors.affiliation: Nora Eccles Harrison Cardiovascular Research and Training Institute, University of Utah, 95 South 2000 East, Salt Lake City, UT 84112-5000, USA. poelzing@cvrti.utah.edu
authors.forename: Steven
authors.initials: S
authors.lastname: Poelzing
authors.forename: Rengasayee
authors.initials: R
authors.lastname: Veeraraghavan
mesh_terms: D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D001145:Arrhythmias, Cardiac / Q000209:etiology* / Q000378:metabolism / Q000503:physiopathology; D017609:Barium Compounds / Q000494:pharmacology*; D002712:Chlorides / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004562:Electrocardiography; D006168:Guinea Pigs; D006329:Heart Conduction System / Q000187:drug effects* / Q000378:metabolism / Q000503:physiopathology; D006352:Heart Ventricles / Q000187:drug effects / Q000378:metabolism; D007008:Hypokalemia / Q000150:complications / Q000378:metabolism* / Q000503:physiopathology; D066298:In Vitro Techniques; D008297:Male; D011188:Potassium / Q000378:metabolism*; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D024661:Potassium Channels, Inwardly Rectifying / Q000037:antagonists & inhibitors* / Q000378:metabolism; D012107:Research Design; D013997:Time Factors
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D026902:Potassium Channel Blockers; D024661:Potassium Channels, Inwardly Rectifying; C024986:barium chloride; D011188:Potassium