Tetramethylammonium activation of muscarinic receptors in cardiac ventricular myocytes.
Tetramethylammonium activation of muscarinic receptors in cardiac ventricular myocytes.
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四甲基铵激活心室肌细胞中的毒蕈碱受体。
DOI：
10.1152/ajpcell.1993.264.6.c1625
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发表时间：
1993
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;Overholt,JL;Wagner,RA;Harvey,RD
用四甲基铵（TMA）替代细胞外Na+可降低豚鼠心室肌细胞中β-肾上腺素能受体刺激激活的Cl-电流的幅度。然而，替代Na+的效果似乎与TMA的存在有关，而不是与Na+的缺乏有关。在不改变Na+浓度的情况下，直接向细胞外溶液中加入TMA，能够以浓度依赖性方式抑制异丙肾上腺素（Iso）激活的Cl-电流。当Cl-电流被1 μ M Iso激活时，引起半数最大抑制的TMA浓度为327 μ M，当Cl-电流被0.03 μ M Iso激活时，引起半数最大抑制的TMA浓度为29 μ M。TMA的作用也被阿托品阻断，表明TMA通过刺激毒蕈碱受体发挥其作用。此外，TMA抑制Iso激活的Ca 2+电流，正如预期的涉及毒蕈碱受体刺激的作用。将Iso的浓度增加1，000倍不能克服TMA对完全Na+置换的反应，并且直接加入TMA能够拮抗使用毛喉素和组胺独立于β-肾上腺素能受体激活的Cl-电流。这些结果与TMA不通过β-肾上腺素能受体的竞争机制发挥作用的假设一致。结论：TMA能够通过激活毒蕈碱受体拮抗腺苷3 '，5'-环一磷酸依赖性的心脏离子通道激活。
Replacement of extracellular Na+ with tetramethylammonium (TMA) reduces the magnitude of the Cl- current activated by beta-adrenergic receptor stimulation in guinea pig ventricular myocytes. However, the effects of replacing Na+ appear to be associated with the presence of TMA, rather than the absence of Na+. Direct addition of TMA to extracellular solutions, without changing the Na+ concentration, was able to inhibit the Cl- current activated by isoproterenol (Iso) in a concentration-dependent manner. The concentration of TMA that caused half-maximal inhibition was 327 microM when the Cl- current was activated by 1 microM Iso and 29 microM when the Cl- current was activated by 0.03 microM Iso. The effect of TMA was also blocked by atropine, suggesting that TMA exerts its effect through stimulation of the muscarinic receptors. Furthermore, TMA inhibited the Iso-activated Ca2+ current, as would be expected for an effect involving muscarinic receptor stimulation. The response to complete Na+ replacement with TMA could not be overcome by increasing the concentration of Iso 1,000-fold, and direct addition of TMA was able to antagonize the Cl- current activated independently of the beta-adrenergic receptor, using forskolin and histamine. These results are consistent with the hypothesis that TMA does not exert its effects through a competitive mechanism at the beta-adrenergic receptor. It is concluded that TMA is able to antagonize adenosine 3',5'-cyclic monophosphate-dependent activation of ion channels in the heart through activation of muscarinic receptors.