Figure 2. K_ATP channel knockout demonstrated disrupted electrical, ionic and metabolic balance precipitating myocardial dysfunction.

A, representative serial tracings from wild-type (WT) and K_ATP channel knockout (KO) illustrate acute elevation of left ventricular pressure upon transverse aortic constriction (TAC) under direct recording compared to preconstriction (Pre). Vertical bar corresponds to 25 mmHg. B, transaortic gradient measured by aortic and left ventricular catheterization demonstrated similar values in WT and KO, under both Pre and TAC conditions. C and D, divergent response to TAC in action potential duration, measured at 90% repolarization (APD₉₀), with shortening in WT and prolongation in KO. Glyburide (Gly; 20 μg g⁻¹, oral), a K_ATP channel inhibitor, replicated the KO phenotype when administered to WT. Treatment of KO with the calcium channel antagonist, verapamil (Ver; 5 μg g⁻¹, i.p.), prior to TAC prevented abnormal action potential prolongation. E, evidence of calcium overload indicated by increased fluorescence intensity in KO cardiomyocytes, but not WT, loaded with the calcium-sensitive probe Fluo-4. F, myocardial energetic deficit in KO versus WT, measured by ATP levels in extracted hearts post-TAC. G and H, left ventricular pressure (LVP) recordings demonstrate myocardial dysfunction with elevation in left ventricular end-diastolic pressure (LVEDP) seen in KO, but not WT or KO pretreated with verapamil. In B, D and H, †P < 0.05 TAC versus pre; in D, E, F and H, *P < 0.05 KO TAC versus WT TAC.