Propranolol이 심근 Mitochondria의 Ca++ 조절작용에 미치는 효과에 관한 연구

Abstract

Propranolol is one of clinically useful antiarrhythmic agents and elcetrophysiologically classified as group II. And the negative inotropic effect which is not related to adrenolytic effect has been demonstrated with high concentration of propranolo l. On the other hand , it has been well known that the calcium plays a central role in excitation-contraction coupling process of myocardium and also in electrophysiological changes of cell membrane. Authors studied the effect of propranolol on calcium uptake and release in mitochondria prepared from porcine myocardium to investigate the mechanism of action of propranolol on myocardium. The results are summerized as follows; 1. The maximum calcium uptake of mitochondria was 50.30 nmoles per mg protein with the rate of 0.65 nmole/mg/sec. and the half-maximum velocity of Ca서-uptake was achieved at about 11. 67μM Caκ 2. The calcium uptake of mitochondria was noncompetitively inhibited by propranolol with dose dependent manner (Ki; 6.2 x lO-'M) . 3. The calcium efflux from the internal pool of mitochondria was rapid by the treatment of 50μM dinitrophenol (9.60 nmole/mg/min.) , andit was not affected by propranolo l. 4. The rate of sodium-induced calcium efflux appeared to be a function of [Na+]' and about 8.80 mM Na+ was required to elicit half-maximum velocity of calcium efflux; The maximum velocity was 7.43 nmole/mg protein per minute 5. The mitochondrial NaηCa얘 exchanges were noncompetitively inhibited by propranolol with dosedependent manner (Ki; 2.91 x lO-'M) . These results suggest that propranolol affects the intracellular calcium homeostasis which may considered to be the mechanism of action of propranolol on myocardium.