Department of Pharmacology, University of Oxford, Oxford, UK.
University of Queensland, Brisbane, Australia.
Sci Rep. 2017 Jan 13;7:40687. doi: 10.1038/srep40687.
In the present study, channelrhodopsin 2 (ChR2) was specifically introduced into murine cells expressing the Phenylethanolamine n-methyltransferase (Pnmt) gene, which encodes for the enzyme responsible for conversion of noradrenaline to adrenaline. The new murine model enabled the identification of a distinctive class of Pnmt-expressing neuroendocrine cells and their descendants (i.e. Pnmt cell derived cells) within the heart. Here, we show that Pnmt cells predominantly localized to the left side of the adult heart. Remarkably, many of the Pnmt cells in the left atrium and ventricle appeared to be working cardiomyocytes based on their morphological appearance and functional properties. These Pnmt cell derived cardiomyocytes (PdCMs) are similar to conventional myocytes in morphological, electrical and contractile properties. By stimulating PdCMs selectively with blue light, we were able to control cardiac rhythm in the whole heart, isolated tissue preparations and single cardiomyocytes. Our new murine model effectively demonstrates functional dissection of cardiomyocyte subpopulations using optogenetics, and opens new frontiers of exploration into their physiological roles in normal heart function as well as their potential application for selective cardiac repair and regeneration strategies.
在本研究中，特定地将通道视紫红质 2（ChR2）引入表达苯乙醇胺 N-甲基转移酶（Pnmt）基因的鼠细胞中，该基因编码负责将去甲肾上腺素转化为肾上腺素的酶。这种新的鼠模型能够鉴定出心脏内独特的一类表达 Pnmt 的神经内分泌细胞及其后代（即 Pnmt 细胞衍生细胞）。在这里，我们表明 Pnmt 细胞主要定位于成年心脏的左侧。值得注意的是，左心房和心室中的许多 Pnmt 细胞似乎基于其形态外观和功能特性而成为工作心肌细胞。这些 Pnmt 细胞衍生的心肌细胞（PdCMs）在形态、电和收缩特性上与传统的心肌细胞相似。通过用蓝光选择性地刺激 PdCMs，我们能够控制整个心脏、分离的组织制剂和单个心肌细胞的心律。我们的新鼠模型有效地展示了使用光遗传学对心肌细胞亚群的功能剖析，并为探索它们在正常心脏功能中的生理作用以及它们在选择性心脏修复和再生策略中的潜在应用开辟了新的前沿。
