Oe H, Xie L H, Horie M
1st Department of Internal Medicine, Osaka University, Japan.
Jpn J Physiol. 1994;44 Suppl 2:S219-26.
The inhibitory pathway of cardiac cAMP-dependent protein kinase regulated Cl- conductance was investigated using the whole-cell configuration of patch-clamp techniques in single guinea pig ventricular myocytes. Pertussis toxin-sensitive G proteins (Gi), mediating the signal transductions between muscarinic receptors and adenylate cyclase, have a substantial tonic activity even in the absence of muscarinic receptor modulators. Muscarinic agonists or antagonists (like atropine) either increase or decrease this basal activity of Gi by altering the proportion of active and inactive forms of the receptors. Similar to L-type Ca-channel currents, the Cl- conductance showed a transient over-recovery upon cessation of brief muscarinic receptor stimulation by carbachol (CCh) (rebound). Atropine alone enhanced the Cl- conductance elicited by low concentrations of Iso (reverse agonist). After washout of atropine, the over-suppression of the conductance was observed as a mirror image of CCh-induced rebound (reverse rebound). Both types of rebound became prominent when cell dialysis with pipette solutions containing 100 microM GTP was minimized with high-resistance pipettes. Endogenous GTP is therefore an intracellular modulator, and not simply a mediator, of Gi-dependent signal transduction.
运用膜片钳技术的全细胞模式，在单个豚鼠心室肌细胞中研究了心脏cAMP依赖性蛋白激酶调节的Cl-电导抑制途径。百日咳毒素敏感的G蛋白（Gi）介导毒蕈碱受体与腺苷酸环化酶之间的信号转导，即使在没有毒蕈碱受体调节剂的情况下也具有显著的张力活性。毒蕈碱激动剂或拮抗剂（如阿托品）通过改变受体活性和非活性形式的比例，增加或降低Gi的这种基础活性。与L型钙通道电流相似，在卡巴胆碱（CCh）短暂刺激毒蕈碱受体停止后，Cl-电导表现出短暂的过度恢复（反弹）。单独使用阿托品可增强低浓度异搏定（反向激动剂）引起的Cl-电导。洗脱阿托品后，观察到电导的过度抑制是CCh诱导反弹（反向反弹）的镜像。当用高电阻移液管将含有100 microM GTP的移液管溶液进行细胞透析减至最小时，两种类型的反弹都变得明显。因此，内源性GTP是Gi依赖性信号转导的细胞内调节剂，而不仅仅是介质。
