Altered beta-adrenergic and muscarinic response of CFTR Cl- current in dialyzed cardiac myocytes.
Altered beta-adrenergic and muscarinic response of CFTR Cl- current in dialyzed cardiac myocytes.
复制标题
改变透析心肌细胞中 CFTR Cl-电流的 β-肾上腺素能和毒蕈碱反应。
DOI：
10.1152/ajpheart.1995.268.5.h1795
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发表时间：
1995
期刊：
影响因子：
--
通讯作者：
Harvey,RD
中科院分区：
文献类型：
--
作者：
Zakharov,SI;Harvey,RD
采用不同构型的全细胞膜片钳技术，研究了不同构型的全细胞膜片钳技术对豚鼠心肌细胞囊性纤维化跨膜电导调节器(CFTR)氯电流的自主调节作用。当使用传统的膜片钳技术记录电流时，在开始透析后，重复暴露于异丙肾上腺素(Iso)长达60分钟，可以继续激活氯电流。然而，氯电流对最大刺激浓度的响应显著减弱。此外，产生氯离子电流半最大激活量(K1/2)的Iso浓度随时间增加。反之，乙酰胆碱抑制异激活电流的K1/2随时间延长而减小。当使用穿孔膜片钳技术记录电流时，对β-肾上腺素能和M受体刺激的敏感性都是稳定的。常规膜片钳技术透析开始后即刻，Iso的敏感性与穿孔膜片钳技术测定的结果几乎相同。然而，最初对毒扁豆碱受体激活的敏感性明显更高。这些结果表明，与传统膜片钳技术相关的细胞透析不仅导致电流幅度的时间依赖性下降，而且还显著改变了离子通道功能的β-肾上腺素能和M受体调节的浓度依赖性。
Autonomic regulation of the cardiac cystic fibrosis transmembrane conductance regulator (CFTR) Cl- current was studied in isolated guinea pig ventricular myocytes using various configurations of the whole cell patch-clamp technique. When currents were recorded using the conventional patch-clamp technique, it was possible to continue to activate the Cl- current on repeated exposure to isoproterenol (Iso) for up to 60 min after initiating dialysis. However, there was significant rundown of the magnitude of the Cl- current response to the maximally stimulating concentrations of Iso. In addition, the concentration of Iso that produced half-maximal activation of the Cl- current (K1/2) increased with time. Conversely, the K1/2 for acetylcholine inhibition of the Iso-activated current decreased with time. When currents were recorded using the perforated patch-clamp technique, the sensitivity to both beta-adrenergic- and muscarinic-receptor stimulation was stable. Immediately after initiation of dialysis with the conventional patch-clamp technique, the sensitivity to Iso was nearly identical to that determined using the perforated patch-clamp technique. However, the initial sensitivity to muscarinic-receptor activation was significantly greater. These results indicate that cell dialysis associated with conventional patch-clamp techniques not only results in a time-dependent rundown of current amplitude, but it also significantly alters the concentration dependence of beta-adrenergic and muscarinic-receptor regulation of ion channel function.