Study On Characteristics Of Sodium-Calcium Exchanger And Potassiumion Channels In Heart Muscle And Finding Of Active Compounds

In recent years, it has been determined that the cardiac Na⁺-Ca²⁺ exchanger plays a prominent role in regulation of intracellular Ca²⁺ homeostasis. Na⁺-Ca²⁺ exchanger located in the plasma membrane is a bi-directional electrogenic ion transporter that couples the translocation of three Na⁺ in one direction with that of one Ca²⁺ in the opposite direction. The forward mode (Ca²⁺ extrusion) of Na⁺-Ca exchanger is the primary Ca efflux mechanism of cardiac myocytes during excitation, however, reverse mode (Ca²⁺ influx) of exchanger is closely related to intracellular Ca²⁺-overload. Recent evidence suggests that reverse mode of Na⁺-Ca²⁺ exchange represents an important pathway in inducing Ca²⁺-overload, particularly during ischemia. During myocardial ischemia and reperfusion, reverse Na⁺-Ca²⁺ exchange activated by increased intracellular Na⁺ result in intracellular Ca²⁺-overload, the latter leads to a series of pathophysiological injuries such as serious arrhythmia, myocardial stunning, and necrosis. Recent observations indicate an early intracellular Na⁺ accumulation during states of anoxia or ischemia and a further increase on reperfusion, which precedes Ca²⁺-overload.We studied the characteristics of Na⁺-Ca²⁺ exchange current (I_Na-ca) in guinea pig ventricular myocytes and effect of SZA, a new compound synthesized by our institute on this current using advanced whole-cell patch clamp techniques.