Figure 3.

Hyperglycaemia-induced arrhythmogenic action potentials are exacerbated by reduced repolarization reserve. (A) High glucose (30 mM, 6 min) induced action potential (AP) changes are enhanced in rabbit ventricular cardiomyocytes pretreated with either 4-aminopyridine (4-AP, 5 mM) to inhibit the transient outward K⁺ current (I_to), pentamidine-analogue 6 (PA-6, 200 nM) to inhibit the inward rectifier K⁺ current (I_K1), E-4031 (1 μM) to inhibit rapid delayed rectifier K⁺ current (I_Kr), HMR-1556 (1 μM) to inhibit slow delayed rectifier K⁺ current (I_Ks), or apamin (100 nM) to inhibit the small-conductance Ca²⁺-activated K⁺ current (I_KCa). Representative traces are shown at 1 Hz steady-state, and insets show tachypacing-induced alternans (S and L refer to short and long AP durations, respectively). (B) AP duration at 90% repolarization (APD₉₀) at 1 Hz steady-state pacing and the magnitude of the tachypacing-induced APD₉₀ alternans at 5 Hz pacing. (C) Representative Poincaré plots of 50 consecutive APD₉₀ values. Statistics on short-term variability (STV) of APD₉₀ at 1 Hz pacing. (At 1 Hz pacing, control: n = 15 cells from seven animals; 4-AP: n = 13 cells from six animals; PA-6: n = 11 cells from five animals; E-4031: n = 10 cells from five animals; HMR-1556: n = 10 cells from five animals; apamin: n = 8 cells from four animals. At 5 Hz pacing, control: n = 15 cells from seven animals; 4-AP: n = 7 cells from four animals; PA-6: n = 11 cells from five animals; E-4031: n = 10 cells from five animals; HMR-1556: n = 9 cells from five animals; apamin: n = 7 cells from four animals.) Nested t-test; NS, non-significant; *P < 0.05, **P < 0.01 vs. 5.5 mM glucose. Nested ANOVA, ^#P < 0.05, ^##P < 0.01, ^###P < 0.001 vs. control.