期刊
CELL CALCIUM
卷 45, 期 1, 页码 38-54出版社
ELSEVIER SCI LTD
DOI: 10.1016/j.ceca.2008.06.003
关键词
TRPC; Cell deformation; SACs; Arrhythmias
类别
资金
- Deutsche Forschungsgemeinschaft [TR02, Is24-19/1]
- Roux Program of the Medical Faculty Halle [12/19]
Cardiomyocytes respond to mechanical stretch with an increase [Ca2+](i). Here, we analyzed which ion channels could mediate this effect. Murine ventricular myocytes were attached to a glass coverslip and a cell-attached glass stylus sheared the upper cell part versus the attached cell bottom. At negative clamp potentials, stretch induced inward currents that increased with the extent of stretch and reversed within 2 min after relaxation from stretch. Stretch activated a nearly voltage-independent GsMTx-4-sensitive non-selective cation conductance G(ns), antibodies against TRPC6 prevented G(ns) activation. In addition, stretch deactivated a Cs+-sensitive inwardly rectifying potassium conductance G(K1), antibodies against Kir2.3 inhibited this effect. Immunolabeling localized TRPC6 and Kir2.3 in T-tubular membranes, and stretch-induced changes in membrane currents were absent in cells whose T-tubules had been removed. In absence of stretch, we could activate G(ns) and deactivate G(K1) by 1-oleoyl-2-acetyl-sn-glycerol (OAG) and other amphipaths. We interpret that the function of TRPC6 and Kir2.3 channels is controlled by both tension and curvature of the surrounding lipid bilayer that are changed by incorporation of amphipaths. Stretch-activation of TRPC6 channels may increase Ca2+ influx directly and indirectly, by membrane depolarization (activation of voltage-gated Ca2+ channels) and by elevated [Na+](i) (augmented Na+,Ca2+-exchange). (C) 2008 Elsevier Ltd. All rights reserved.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据