The role of calcium in cellular dysfunction.
In order to study the effects of substances with selective Ca2+ entry blocking properties which enhance the tolerance to ischemia by preventing a toxic calcium overload, attempts are made to localize calcium ultrastructurally. Under normoxic conditions, a mobile pool of Ca2+ is localized in synaptic vesicles and in mitochondria of brain cells; in mitochondria of cardiac, skeletal and vascular smooth muscle; and in the junctional SR of fast skeletal muscle. A plasmalemmabound pool of Ca2+ is present in cardiac and slow skeletal muscle. Ischemia or hypoxia induce marked shifts in calcium of both the mobile and the plasmalemma-bound pools. Cardiac and skeletal muscle mitochondria scavenge huge amounts of calcium, especially during the reperfusion period following prolonged circulatory arrest. The membrane-bound Ca2+ is lost under these conditions. In the hypoxic brain, the amount of intracellular calcium clearly parallels the degree of damage. Observations made on peripheral and brain blood vessels show that high amounts of precipitated Ca2+ cover the myofilaments upon induction of spasm. The antispasmodic effect of the selective Ca2+-entry blockers flunarizine and lidoflazine is morphologically characterized by the absence of Ca2+ over the myofilaments in muscle treated as such whereas the extracellular Ca2+ remained the same. This observation indicates that the entry of Ca2+ is blocked at the level of the plasma membrane. In the heart and brain these drugs preserve the structural integrity of the plasmalemma-surface coat complex and thereby protect the cells against the devastating consequences of cellular calcium overload.
D000818:Animals; D001921:Brain / Q000098:blood supply; D002545:Brain Ischemia / Q000378:metabolism* / Q000503:physiopathology; D002118:Calcium / Q000032:analysis / Q000502:physiology*; D002121:Calcium Channel Blockers / Q000378:metabolism; D002534:Hypoxia, Brain / Q000378:metabolism / Q000503:physiopathology; D008928:Mitochondria / Q000378:metabolism; D009206:Myocardium / Q000378:metabolism; D012377:Rodentia
D002121:Calcium Channel Blockers; D002118:Calcium