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Properties and regulation of cardiac chloride current

心氯电流的特性和调节

基本信息

批准号：
03454132
负责人：
EHARA Tsuguhisa
金额：
$ 3.07万
依托单位：
Saga Medical School
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1991
资助国家：
日本
起止时间：
1991 至 1992
项目状态：
已结题

项目摘要

1. Study of whole cell c1^- current (guinea-pig ventricular and atrial cells). (1) beta-adrenergic and muscarinic regulation of C1^- current (I_<Cl>). Acetylcholine (ACh) depressed the I_<Cl> induced by beta-adrenergic stimulation. ACh also suppressed the I_<Cl> induced by forskolin, but failed to interfere with the one induced by internal application of cyclic AMP. ACH appears to inhibit the beta-receptor-dependent I_<Cl> by deactivating adenylate cyclase through inhibitory G protein. (2) Activation of I_<Cl> by purinergic stimulation. Extracellular application of ATP at muM levels was found to activate a time-independent current very similar to the beta-receptor-dependent I_<Cl>. The relationship between the reversal potential of this current and [Cl]_0 indicated that this current is also a Cl^- current. ADP, AMP, and adenosine were also effective in inducing the I_<Cl>, showing no clear order of potency for the purinoceptor subtypes involved.2. Study of single C1^- channel (guinea-pig ventricular cells). Cell-attached patch clamp was performed to record single Cl^- channel cur-rents, while the cells were dialyzed with cyclic AMP-containing internal solution through a second pipette. The activity of C1^- channel appeared in some patches during the cell dialysis. Analysis of the open probability (P_0) of the channels, with regard to the P_0 value at their appearance and any changes in P_0 during cell dialysis, suggested that cyclic AMP system make the 'latent' C1^- channels available without influencing their own kinetic behaviour. The channel Seemed to have at least one open state and two closed states; the open time histograms showed one exponential component with a time constant of about 1 s, while the closed time histograms showed two exponential components with time constants of about 0.2 and 1 s. These time constants showed no clear voltage-dependence.

1.全细胞c1^-电流的研究（豚鼠心室和心房细胞）。(1)C1^-电流（I_）的β-肾上腺素能和毒蕈碱调节<Cl>。乙酰胆碱（ACh）可抑制<Cl>β-肾上腺素能刺激引起的I_2。ACh也抑制Forskolin引起的I_2<Cl>，但不干扰cAMP引起的I_2。ACH通过<Cl>抑制性G蛋白使腺苷酸环化酶失活，从而抑制β受体依赖性I_2。(2)通过<Cl>嘌呤能刺激激活I_2。细胞外应用μ M水平的ATP可激活与β受体依赖性I_2非常相似的非时间依赖性电流<Cl>。该电流的反转电位与[Cl]_0的关系表明该电流也是Cl^-电流。ADP、AMP和腺苷也能有效地诱导I_2，<Cl>但没有明确的嘌呤受体亚型的效力顺序.单个C1^-通道的研究（豚鼠心室细胞）。细胞贴附膜片钳记录单个Cl^-通道电流，同时通过第二根移液管用含环AMP的内溶液透析细胞。在细胞透析过程中，部分斑片出现C1^-通道活性。对通道开放概率（P_0）的分析，考虑到通道出现时的P_0值和细胞透析期间P_0的任何变化，表明环AMP系统使“潜伏”C1^-通道可用，而不影响其自身的动力学行为。通道似乎具有至少一个开放状态和两个关闭状态;开放时间直方图显示时间常数约为1 s的一个指数分量，而关闭时间直方图显示时间常数约为0.2和1 s的两个指数分量。这些时间常数没有明显的电压依赖性。