【摘要】 目的:研究腺苷对豚鼠心室肌细胞内游离钙浓度([Ca2+]i)的影响并探讨其可能机制。方法:用激光共聚焦显微镜探测细胞内游离钙浓度,结果用相对荧光强度((FI-FI0)/FI0,%;FI0:对照;FI:给药)表示。结果:①在正常台氏液和无钙台氏液中,腺苷(10,50,100μmol/L)浓度依赖性地降低[Ca2+]i。②含30mmol/L KCl的台氏液(高钾台氏液)能够增加[Ca2+]i。腺苷(10,50,100μmol/L)能够显著抑制KCl引起的[Ca2+]i的增加。③预先应用选择性腺苷A1受体拮抗剂DPCPX(1μmol/L),可大部分取消腺苷(100μmol/L)在高钾台氏液中的作用。腺苷(100μmol/L)在高钾台氏液的作用也可被预先应用一氧化氮(NO)合酶抑制剂L-NAME(1mmol/L)所部分减弱。④腺苷(100μmol/L)能明显抑制无钙台氏液中由低浓度ryanodine引起的[Ca2+]i增加。⑤当细胞外液钙浓度由1mmol/L增加到10mmol/L而诱发心室肌细胞钙超载时,部分心室肌细胞产生可传播的钙波,腺苷(100μmol/L)可降低钙波发生的频率和持续时间,最终阻断钙波并降低[Ca2+]i。结论:腺苷可通过抑制外钙内流和减少肌浆网内钙释放从而降低[Ca2+]i,其减少外钙内流可能是由于腺苷A1受体介导的电压依赖性Ca2+通道的抑制,NO可能参与这一过程。更多还原

【Abstract】 Aim: To observe the effects of adenosine on intracellular calcium conc entration(Ca²⁺ _i) level in guinea pig ventricular myocytes and to def ine the possible mechanisms involved. Methods: The effects of ad enosine on Ca²⁺ _i were investigated in guinea pig ventricular myocyte s. Ca²⁺ _i was detected by laser confocal microscopy and represented b y relative fluorescent intensity（（FI-FI₀）/FI₀, %, FI₀: control, FI: admi nistration of drugs ）. Results: ① Adenosine（10, 50, 100 μmol/L ） reduced Ca²⁺ _i of ventricular myocytes in both normal Tyrode’s solut ion and Ca （2+）-free Tyrode’s solution in a concentration-dependent manner. ② Tyrode’s solution containing 30 mmol/L KCl（high K⁺ Tyrode’s solution ） in duced Ca 2+ _i elevation in ventricular myocytes, while adenosine（10, 5 0, 100 μmol/L） markedly inhibited the increase in Ca 2+ _i induced by KCl. ③ Pretreatment with DPCPX（1 μmol/L ） significantly reduced the effects of adenosine（100 μmol/L ） in high K⁺ Tyrode’s solution. The effects of adenos ine（100 μmol/L ） on Ca 2+ _i in high K⁺ Tyrode’s solution were also partially attenuated by pretreatment with L-NAME（1 mmol/L）. ④ Adenosine（10 0 μmol/L） markedly inhibited the low concentration of ryanodine-induced Ca²⁺ _i increase in Ca²⁺-free Tyrode’s solution. ⑤ When the propagatin g waves of elevated Ca²⁺_i (Ca²⁺ waves ) were produced by incre asing extracellular Ca²⁺concentration from 1 mmol/L to 10 mmol/L, adenosi ne（100 μmol/L） could block the propagating waves of elevated Ca²⁺ i, reduce the frequency and duration of pro-pagating waves, and reduce Ca²⁺ _i as well. Conclusion: Adenosine may reduce the Ca （2+） _i in isolated guinea pig ventricular myocytes via inhibiting Ca²⁺ in flux and alleviating Ca²⁺ release from sarcoplasmic reticulum（SR）. The re duction of Ca²⁺ influx might be due to the inhibition of voltage-depende nt Ca ²⁺ channel via adenosine A₁ receptor, and NO might be involved in t his process.更多还原