Experimental Physiology Laboratory (EPhyL), Antofagasta Institute, Universidad de Antofagasta, Antofagasta, Chile.
Laboratory of Neurobiology, Department of Biomedicine, Universidad de Antofagasta, Antofagasta, Chile.
Am J Trop Med Hyg. 2018 Jan;98(1):105-112. doi: 10.4269/ajtmh.17-0293.
, the etiological agent of Chagas diseases, invades the cardiac tissue causing acute myocarditis and heart electrical disturbances. In invasion, the parasite induces [Ca] transients in the host cells, an essential phenomenon for invasion. To date, knowledge on the mechanism that elicits transients of [Ca] during the infection of cardiac myocytes has not been fully characterized. Pannexin1 (Panx1) channel are poorly selective channels found in all vertebrates that serve as a pathway for ATP release. In this article, we demonstrate that infection results in the opening of Panx1 channels in cardiac myocytes. We show that pharmacological blockade of Panx1 channels inhibits -induced [Ca] transients and invasion in cardiac myocytes. Our results indicate that opening of Panx1 channels are required for invasion in cardiac myocytes, and we propose that targeting Panx1 channel could provide new potential therapeutic approaches to treat Chagas disease.
克氏锥虫，恰加斯病的病原体，侵袭心肌组织，导致急性心肌炎和心脏电活动紊乱。在感染过程中，寄生虫会在宿主细胞中诱导钙离子瞬变，这是感染的必要现象。迄今为止，对于感染心肌细胞过程中引发钙离子瞬变的机制还没有完全阐明。缝隙连接蛋白 1（Panx1）通道是在所有脊椎动物中发现的非选择性通道，可作为 ATP 释放的途径。本文中，我们证明了克氏锥虫感染会导致心肌细胞中 Panx1 通道的打开。我们发现，药理学阻断 Panx1 通道可抑制 诱导的钙离子瞬变和心肌细胞的侵袭。我们的结果表明，Panx1 通道的打开对于心肌细胞中的克氏锥虫感染是必需的，我们提出靶向 Panx1 通道可能为治疗恰加斯病提供新的潜在治疗方法。
