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作 者:马会杰[1] 董梅[2] 吉恩生[1] 王川[3] 尹京湘[1] 王庆山[1]
机构地区:[1]河北医科大学基础医学研究所生理室,河北石家庄050017 [2]河北科技大学校医院,河北石家庄050054 [3]河北医科大学基础医学研究所药理室,河北石家庄050017
出 处:《中国应用生理学杂志》2006年第1期58-62,i0007,共6页Chinese Journal of Applied Physiology
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。Aim: To observe the effects of adenosine on intracellular calcium concentration( [ Ca^2+ ]i) level in guinea pig ventricular myocytes and to define the possible mechanisms involved. Methods: The effects of adenosine on [ Ca^2+ ]i were investigated in guinea pig ventricular myocytes. [ Ca^2+] i was detected by laser confocal microscopy and represented by relative fluorescent intensity((FI-FI0)/Flo,% , FI0 : control, FI: administration of drugs ). Results: ① Adenosine(10, 50, 100μmol/L ) reduced [Ca^2+ ]i of ventricular myocytes in both normal Tyrode's solution and Ca^2+ -free Tyrode's solution in a concentration-dependent manner. @) Tyrode's solution containing 30 mmol/L KCI( high K^+ Tyrode' s solution ) induced [ Ca^2 + l i elevation in ventricular myocytes, while adenosine( 10, 50, 100μmol/L) markedly inhibited the increase in [ Ca^2 + ]i induced by KCl.③ Pretreatment with DPCPX( 1μmol/L ) significantly reduced the effects of adenosine(100 μmol/L ) in high K+ Tyrode's solution. The effects of adenosine(100μmol/L ) on [Ca^2+ ]i in high K+ Tyrode's solution were also partially attenuated by pretreatment with L-NAME( 1mmol/L). ④Adenosine( 100μmol/L) markedly inhibited the low concentration of ryanodine-induced [ Ca^2+ ]i increase in Ca^2+ -free Tyrode's solution. ⑤ When the propa-gating waves of elevated [Ca^2+ ]i(Ca^2+ waves ) were produced by increasing extracellular Ca^2+ concentration from 1mmol/L to 10mmol/L, adenosine( 100μmol/L) could block the propagating waves of elevated [Ca^2+]i, reduce the frequency and duration of propagating waves, and reduce [Ca^2+]i as well. Conclusion: Adenosine may reduce the [Ca^2+]i in isolated guinea pig ventricular myocytes via inhibiting Ca^2+ influx and alleviating Ca^2 + release from sarcoplasmic reticulum(SR). The reduction of Ca^2 + influx might be due to the inhibition of voltage-dependent Ca^2 + channel via adenosine Al recept
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