Effects of angiotensin II on transient receptor potential melastatin 7 channel function in cardiac fibroblasts

Abstract

The aim of the present study was to investigate the electrophysiological properties of transient receptor potential melastatin 7 (TRPM7) channels in the cell membranes of cardiac fibroblasts (CFs). CFs obtained from Sprague-Dawley rats were treated with six different concentrations of angiotensin (Ang) II for 12 h. The optimum concentration of Ang II for inducing fibrosis was selected by measuring collagen protein expression levels at each concentration. The optimum concentration of Ang II was then used to treat the CFs at five different time-points, and the TRPM7 current across the CF membranes was recorded along with the collagen protein levels in each group. The optimum Ang II concentration for inducing fibrosis was found to be 1 nmol/l; when it was administered to CFs at 0, 6, 12, 24 and 48 h, the protein expression levels of TRPM7 and collagen III initially increased, reaching maximum levels at 12 h, and then decreased. This result positively correlated with the TRPM7 current levels on either side of the CF membranes: The TRPM7 current under the effect of the optimal Ang II concentration for inducing fibrosis was initially increased and then later decreased. This is one of the key mechanisms by which Ang II mediates the proliferation and apoptosis of CFs. This knowledge may be used to identify treatments for the prevention of cardiac fibrosis.