Properties and regulation of cardiac chloride current

1. 全细胞c1^-电流（豚鼠心室和心房细胞）的研究。(1) β -肾上腺素能和毒蕈碱调节C1^-电流（I_<Cl>）。乙酰胆碱（ACh）抑制β -肾上腺素能刺激引起的I_<Cl>。ACh还能抑制福斯克林诱导的I_<Cl>，但不能干扰内服环AMP诱导的I_<Cl>。ACh似乎通过抑制G蛋白使腺苷酸环化酶失活，从而抑制β受体依赖性I_<Cl>。(2)嘌呤能刺激I_<Cl>的激活。细胞外应用muM水平的ATP可以激活一个与时间无关的电流，这与β受体依赖的I_<Cl>非常相似。该电流的反转电位与[Cl]_0的关系表明，该电流也是一个Cl^-电流。ADP、AMP和腺苷也能诱导I_<Cl>，但对嘌呤受体亚型没有明确的效力顺序。单C1 -通道（豚鼠心室细胞）的研究。细胞贴附膜片钳记录单个Cl^-通道电流，同时细胞通过第二个移液管与含有环状amp的内溶液透析。在细胞透析过程中，部分斑块出现了C1^-通道的活性。通过分析通道的开放概率（P_0），以及通道出现时的P_0值和细胞透析过程中P_0的任何变化，表明环AMP体系使“潜在”的C1^-通道可用，而不影响其自身的动力学行为。通道似乎至少有一个开放状态和两个封闭状态；开放时间直方图显示一个指数分量，时间常数约为1 s；封闭时间直方图显示两个指数分量，时间常数约为0.2和1 s。这些时间常数没有明显的电压依赖性。

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.