低氧后心肌钙瞬变变化与β-肾上腺素受体脱敏的关系

目的:慢性低氧时,心脏对β-肾上腺素受体激动的反应出现脱敏现象,细胞内钙Ca²⁺]_i瞬变的幅度降低、时程延长,本研究观察上述变化在低氧时发生和发展的时间过程和对应关系。方法:在年龄对等的正常及慢性低氧1d、3d、1周、2周、3周、4周和8周的大鼠,分别分离正常及慢性低氧条件下的心室肌细胞,以Fura-2为Ca²⁺]_i的指示剂,用光谱荧光法测定心肌细胞的Ca²⁺]_i瞬变及其对心肌β-受体激动后反应的变化。结果:在低氧1d、3d、1周等时间内,电刺激引起的Ca²⁺]_i瞬变、咖啡因引起的Ca²⁺]_i瞬变及电刺激引起的Ca²⁺]_i瞬变对β-受体激动剂异丙肾上腺素的增加反应无明显变化;在低氧2周以上时,电刺激引起的Ca²⁺]_i瞬变的幅度开始降低,而时程开始延长,其对异丙肾上腺素的反应也开始降低。咖啡因引起的Ca²⁺]_i瞬变幅度也开始降低;在低氧3周和4周时,上述变化程度逐渐加重;在低氧8周时各参数的变化有所恢复,但与4周时的变化程度无明显差异。结论:低氧2-4周时,心脏的β-肾上腺素受体发生脱敏现象,脱敏的机制与3种调节Ca²⁺]_i瞬变的蛋白质:L-型钙通道、ryanodine受体操纵的钙通道和钙泵等活性的降低有关,后者也可能是低氧时心脏功能降低的重要机制。低氧4-8周时,心脏对低氧产生了适应和代偿。

β-adrenoceptor desensitization and changes of calcium transient in rat ventricular myocytes following chronic hypoxia

AIM:The present study was to investigate the time course of β-adrenoceptor desensitization and changes in the calcium transient in rat ventricular myocytes following chronic hypoxia.METHODS: With the spectrofluorometric method, the intracellular calcium( Ca²⁺]_i) transient and its response to β-adrenoceptor stimulation were determined in the single right ventricular myocytes, loaded with Fura-2. RESULTS:After 2-3 weeks of chronic hypoxia, the amplitudes of electrically induced Ca²⁺]_i transient and caffeine-induced Ca²⁺]_i transient started to decrease and the duration of Ca²⁺]_i transient prolonged. The enhanced electrically induced Ca²⁺]_i transient evoked by isoprotrenol was also decreased. After 3 or 4 weeks of chronic hypoxia, these changes aggravated gradually. After 8 weeks of chronic hypoxia, the changes of all these parameters were convalescent, meanwhile there was no significant difference compared with that of 4 weeks group.CONCLUSIONS:After 2-4 weeks of chronic hypoxia,theβ-adrenoceptor desensitization occurs,the underlying mechanism is related to the decreased function of L-type of calcium channel,ryan odine receptor-operated calcium channel and calcium ATPase,which is responsible for the decreased cardiac functionl. At 8 weeks of hypoxia,the heart is in adaptation and compensatory process.