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

AIMS: 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 (KATP) channels.

MATERIALS AND

METHODS

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. KATP currents (IKATP) in ventricular myocytes were recorded using the whole-cell patch clamp technique.

KEY FINDINGS: 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 KATP 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 IKATP by CST, which was fully suppressed by Gli.

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