Beta‐adrenergic and muscarinic regulation of the chloride current in guinea‐pig ventricular cells.
Beta‐adrenergic and muscarinic regulation of the chloride current in guinea‐pig ventricular cells.
复制标题
豚鼠心室细胞氯电流的β-肾上腺素能和毒蕈碱调节。
DOI：
10.1113/jphysiol.1991.sp018705
复制
发表时间：
1991
期刊：
影响因子：
--
通讯作者：
T. Ehara
中科院分区：
文献类型：
--
作者：
F. M. Tareen;K. Ono;A. Noma;T. Ehara
1.采用膜片钳法结合移液器灌注技术对单个豚鼠心室细胞进行电压钳。电压依赖的电流系统大部分被阻断，并且通过施加斜坡脉冲来测量背景膜电导。 2. β-肾上腺素能效应物和相关物质，如肾上腺素、异丙肾上腺素、毛喉素或内部应用环 AMP 诱导电流分量，该电流分量显示出接近预期 Cl-平衡电位的反转电位以及 I-V 关系中的向外整流。这表明该 Cl 电流的激活是由于环 AMP 依赖性蛋白激酶对通道蛋白或相关结构的磷酸化所致。随着Cl-电流的激活，细胞的膜电容可逆地降低。 3.乙酰胆碱（ACh）抑制β-肾上腺素能刺激和毛喉素诱导的反应，但不能干扰环磷酸腺苷诱导的反应。 4. 异丙肾上腺素或毛喉素激活 Cl 电流的剂量依赖性通过 Hill 方程拟合，异丙肾上腺素的系数为 1.9，半最大浓度 K 1/2 = 13 nM，毛喉素的 Hill 系数为 3，K 1/2 = 1.2 µM。在 5.5 microM-ACh 存在的情况下，剂量反应关系转向更高剂量；异丙肾上腺素的 K 1/2 为 65 nM，毛喉素的 K 1/2 为 3.6 microM。 5. 在异丙肾上腺素存在的情况下洗掉乙酰胆碱经常会导致反应短暂的超调。当使用饱和浓度的异丙肾上腺素时，没有观察到这种反弹。 6.内服环化GMP可增强异丙肾上腺素或肾上腺素引起的Cl电流反应。 7. 当内用环磷酸腺苷时，大多数细胞的反应很小。当细胞灌注 20 microM-IBMX（3-异丁基-1-甲基黄嘌呤）时，循环 AMP 的应用始终诱导 Cl-电流。这表明磷酸二酯酶活性强烈缓冲环 AMP 通过膜片移液器吸头的流入。 8. 我们认为，β-肾上腺素能刺激和毒蕈碱抑制之间的补偿性相互作用是在膜水平上，最有可能是通过 GTP 结合蛋白激活腺苷酸环化酶。
1. Single guinea‐pig ventricular cells were voltage clamped using the patch clamp method combined with the pipette‐perfusion technique. The voltage‐dependent current systems were mostly blocked, and the background membrane conductance was measured by applying ramp pulses. 2. beta‐Adrenergic effectors and related substances such as adrenaline, isoprenaline, forskolin or internal application of cyclic AMP induced a current component which showed a reversal potential near the expected Cl‐ equilibrium potential as well as an outward rectification in the I‐V relation. It is suggested that the activation of this Cl‐ current was due to phosphorylation of the channel protein or related structure by the cyclic AMP‐dependent protein kinase. Coincidentally with the activation of the Cl‐ current, the membrane capacitance of the cell decreased reversibly. 3. Acetylcholine (ACh) depressed the responses induced by beta‐adrenergic stimulation and forskolin, but failed to interfere with the one induced by cyclic AMP. 4. The dose dependence of the Cl‐ current activation by isoprenaline or forskolin was fitted by the Hill equation, with a coefficient of 1.9 and a half‐maximum concentration K 1/2 = 13 nM for isoprenaline, and with a Hill coefficient of 3 and a K 1/2 = 1.2 microM for forskolin. In the presence of 5.5 microM‐ACh the dose‐response relation shifted to higher doses; K 1/2 was 65 nM for isoprenaline and 3.6 microM for forskolin. 5. Washing out ACh in the presence of isoprenaline frequently caused transient overshoots of the response. When a saturating concentration of isoprenaline was used, this rebound was not observed. 6. The internal application of cyclic GMP enhanced the response of the Cl‐ current induced by isoprenaline or adrenaline. 7. When cyclic AMP was applied internally, the response was small in most cells. When the cell was superfused with 20 microM‐IBMX (3‐isobutyl‐1‐methylxanthine), the Cl‐ current was consistently induced by the application of cyclic AMP. It is suggested that phosphodiesterase activity strongly buffered the influx of cyclic AMP through the patch pipette tip. 8. We suggest that the compensatory interaction between the beta‐adrenergic stimulation and the muscarinic inhibition is at the membrane level, most probably via GTP‐binding proteins in activating adenylate cyclase.
通过双重 G 蛋白途径抑制心脏钠通道的 β 肾上腺素能。
DOI：
10.1126/science.2547248
发表时间：
1989
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Schubert,B;VanDongen,AM;Kirsch,GE;Brown,AM
通讯作者：
Brown,AM
影响因子：
5.5
作者：
FISCHMEISTER, R;HARTZELL, HC
通讯作者：
HARTZELL, HC