The possible role of endogenous amphiphiles in the membrane abnormalities of ischemic and reperfused myocardium.
Calcium entry into cardiac cells is believed to be controlled by transmembrane-voltage dependent, protein regulated "channels." The sarcoplasmic reticulum participates in the regulation of cytosolic calcium by ATP dependent Ca2+ sequestration during diastole, and by action potential stimulated calcium release. Massive calcium overloading occurs during reperfusion following myocardial ischemia. Calcium overloading activates phospholipases, which may activate another mechanism involved in lethal cellular injury, that is, the accumulation of long chain fatty acids and their derivatives. These compounds are soluble amphiphiles, and once liberated, they may insert into biological membranes and change membrane composition, physiology, and response to ions and drugs. Sarcoplasmic reticulum vesicles were used as an in vitro model to study the effects of palmitic acid, oleic acid, and palmitylcarnitine on the ability of this membrane system to sequester calcium within the vesicles. In the absence of phosphate, palmitic acid enhanced the ability of the vesicles to sequester calcium. Oleic acid and palmitylcarnitine inhibited calcium sequestration. In the presence of phosphate palmitic acid also inhibited the sequestration of calcium by sarcoplasmic reticulum, although not as severely as oleic acid and palmitylcarnitine. These results suggest that the disturbances in cellular calcium homeostasis following ischemia may be due, in part, to the incorporation of accumulated long chain fatty acids into membranes.
D000818:Animals; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002462:Cell Membrane / Q000378:metabolism; D003326:Coronary Circulation; D003327:Coronary Disease / Q000378:metabolism*; D005227:Fatty Acids / Q000378:metabolism* / Q000502:physiology; D019301:Oleic Acid; D009829:Oleic Acids / Q000378:metabolism / Q000502:physiology; D010168:Palmitates / Q000378:metabolism / Q000502:physiology; D011817:Rabbits; D012519:Sarcoplasmic Reticulum / Q000378:metabolism / Q000502:physiology
D005227:Fatty Acids; D009829:Oleic Acids; D010168:Palmitates; D019301:Oleic Acid; D002118:Calcium