Department of Cellular Physiology, Ruhr-University Bochum, 44780 Bochum, Germany.
J Biol Chem. 2011 Jan 7;286(1):290-8. doi: 10.1074/jbc.M110.163477. Epub 2010 Nov 1.
A large conductance (∼300 picosiemens) channel (LCC) of unknown molecular identity, activated by Ca(2+) 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 Ca(2+) release can trigger action potentials, suggesting that Panx1 channels potentially promote arrhythmogenic activities.
先前在分离的心肌细胞中描述了一种未知分子身份的大电导（~300 皮西门子）通道（LCC），该通道由肌浆网释放 Ca（2+）激活，特别是在咖啡因增强时。该通道的一个潜在候选物是连接蛋白 1（Panx1），当在非洲爪蟾卵母细胞和哺乳动物细胞中表达时，它已被证明能形成大离子通道。Panx1 的功能涉及到 ATP 介导的自分泌/旁分泌信号转导，并且在几种细胞死亡途径中起着关键作用。在这里，我们证明在培养 4 天后，心肌细胞中不再检测到 LCC 活性，但可以通过腺病毒基因转移 Panx1 来挽救。内源性 LCC 及其与 Panx1 表达相关的 LCC 具有先前用于鉴定和表征 Panx1 通道的关键药理学特性。这些数据表明 Panx1 构成了心肌细胞的 LCC。在没有 Ca（2+）释放的情况下，单个 Panx1 通道的偶发性开放可以触发动作电位，表明 Panx1 通道可能促进心律失常活动。
