Figure 12.

Electrophysiological features contributing to arrhythmogenesis in hypokalemic murine ventricles. A: outward and inward K⁺ currents (a, c) and representations of their respective maximum currents (b, d) from whole cell patch-clamped epicardial (a, b) and endocardial myocytes (c, d) under normokalemic (dark lines) and hypokalemic (3 mM) conditions (pale lines). Under normokalemic conditions, epicardial myocytes (a) showed greater early outward I_K than endocardial myocytes (c). However, whereas hypokalemia reduced early outward I_K in epicardial but not endocardial cells (b), it reduced inward I_K1 in epi- and endocardial cells by similar extents (b, d). B: monophasic AP recordings from LV endocardial and epicardial Langendorff-perfused WT murine hearts paced at 125 ms BCL, under control (5.2 mM [K⁺]; a) and hypokalemic conditions (3 mM [K⁺]; b). C: steady-state epicardial (white columns) and endocardial APD₉₀s (gray columns) and the resulting ΔAPD₉₀ (black columns) at [K]_o = 5.2 mM (a), 4 mM (b), and 3 mM (c), respectively. D: programmed electrical stimulation (PES) of isolated, WT Langendorff-perfused mouse hearts under normokalemic (a) and hypokalemic 4 mM (b) and 3 mM [K⁺]_o (c) conditions did not induce VT in (a) but induced VT in 2 of 7 hearts in 4 mM [K⁺]_o (b) and 9 of 11 hearts in 3 mM [K⁺]_o (c). E: LV epicardial monophasic action potential (MAP) recordings during intrinsic pacing (a), and programmed electrical stimulation (PES) (b) in the presence of 3 mm [K⁺]_o and 2 μm KN-93. KN-93 reduced the occurrence of early afterdepolarizations (EADs), triggered beats and ventricular tachycardia (VT) in spontaneously beating hearts (a). It failed to protect against arrhythmia provoked by PES in 6 of 6 hearts (b). [From Killeen and co-workers (559, 561).]