Pannexin 1 Constitutes the Large Conductance Cation Channel of Cardiac Myocytes
Pannexin 1 Constitutes the Large Conductance Cation Channel of Cardiac Myocytes
复制标题
DOI：
10.1074/jbc.m110.163477
复制
发表时间：
2011-01-07
影响因子：
4.8
通讯作者：
Zoidl, Georg
中科院分区：
文献类型：
--
作者：
Kienitz, Marie-Cecile;Bender, Kirsten;Zoidl, Georg
先前已在分离的心肌细胞中描述了分子身份未知的大电导通道（LCC），该通道由肌浆网释放的 Ca2+ 激活，特别是在咖啡因增强时。该通道的一个潜在候选者是pannexin 1 (Panx1)，它已被证明在非洲爪蟾卵母细胞和哺乳动物细胞中表达时可形成大离子通道。 Panx1 功能与 ATP 介导的自体/旁分泌信号传导有关，并且在多种细胞死亡途径中发挥着至关重要的作用。在这里，我们证明培养 4 天后，肌细胞中不再检测到 LCC 活性，但可以通过 Panx1 的腺病毒基因转移来挽救。内源性 LCC 和与 Panx1 表达相关的 LCC 具有先前用于识别和表征 Panx1 通道的关键药理学特性。这些数据表明Panx1构成心肌细胞的LCC。在没有 Ca2+ 释放的情况下，单个 Panx1 通道的零星开放可以触发动作电位，表明 Panx1 通道可能促进致心律失常活动。
A large conductance (similar to 300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca2+ release from the sarcoplasmic reticulum, particularly when augmented by caffeine, has been described previously in isolated cardiac myocytes. A potential candidate for this channel is pannexin 1 (Panx1), which has been shown to form large ion channels when expressed in Xenopus oocytes and mammalian cells. Panx1 function is implicated in ATP-mediated auto-/paracrine signaling, and a crucial role in several cell death pathways has been suggested. Here, we demonstrate that after culturing for 4 days LCC activity is no longer detected in myocytes but can be rescued by adenoviral gene transfer of Panx1. Endogenous LCCs and those related to expression of Panx1 share key pharmacological properties previously used for identifying and characterizing Panx1 channels. These data demonstrate that Panx1 constitutes the LCC of cardiac myocytes. Sporadic openings of single Panx1 channels in the absence of Ca2+ release can trigger action potentials, suggesting that Panx1 channels potentially promote arrhythmogenic activities.