Catestatin improves cardiac function during ischemia/reperfusion via activation of ATP-sensitive potassium channel in...

This study aimed to investigate the cardioprotective effects of catestatin (CST) against ischemia/reperfusion (I/R) injury and the potential involvement of ATP-sensitive potassium (K_ATP) channels.

In vivo I/R was induced in adult male Sprague-Dawley rats by left anterior descending coronary artery ligation followed by reperfusion. Cardiac function and blood pressure were continuously recorded. Infarct area was quantified using Evans blue/TTC staining. Optical mapping was used to evaluate myocyte calcium transients of hearts. Ventricular myocyte contractility was measured using an edge-detection system. Action potentials in papillary muscle were recorded by intracellular microelectrodes. K_ATP currents (IK_ATP) in ventricular myocytes were recorded using the whole-cell patch clamp technique.

We demonstrated that CST preserved cardiac function during I/R, significantly attenuating declines in left ventricular systolic pressure, heart rate, and arterial pressures. CST markedly reduced infarct area and decreased arrhythmia scores, which were abolished by glibenclamide (Gli), a K_ATP channel inhibitor. At the cellular level, CST reduced sarcomere shortening amplitudes and maximal rates of shortening and relengthening. Optical mapping showed that CST prolonged calcium transient activation and durations without change in amplitude. Furthermore, CST selectively shortened APD₅₀ and APD₉₀, while Gli reversed the shortening of APD. Patch clamp experiments revealed a concentration-dependent augmentation of IK_ATP by CST, which was fully suppressed by Gli.

CST protects against myocardial I/R injury and arrhythmias by activating K_ATP channels. These findings identify that myocyte K_ATP channels mediate CST-induced cardioprotection and may serve as a promising translational target for ischemic heart disease treatment.