Role of sarcolemmal ATP-dependent K⁺ channels in cardiac ischemic injury

Abstract

In the normoperfused heart, Ca²⁺ enters the myocardial cell through voltagedependent Ca²⁺ channels and is extruded through the sarcolemmal Ca²⁺ pump and the Na+/Ca²⁺ exchanger. During ischemia and early reperfusion, however, sarcoplasmic reticulum reuptake and sarcolemmal Ca²⁺ pump activities are impaired due to decreased ATP. In addition, owing to defective Na⁺-K⁺ pump performance and low pH favoring Na⁺ entry in exchange for H⁺ output through the Na⁺/H⁺ exchanger, the Na⁺/Ca²⁺ exchanger operates in its reverse mode incorporating Ca²⁺ to diminish increased intracellular Na⁺. Thus, the resulting impaired Ca²⁺ balance produces Ca²⁺ overload and myocardial injury probably by activation of Ca²⁺-dependent proteases which can partially destroy contractile proteins leading to decreased responsiveness of contractile filaments to Ca²⁺ (18). This chain of ischemic events is in part counteracted by activation of ATP-dependent K⁺ (KATP) channels which by allowing earlier passive K⁺ output, shortens action potential duration and reduces the time during which Ca²⁺ can enter the cell.