IP3R and RyR calcium channels are involved in neonatal rat cardiac myocyte hypertrophy induced by tumor necrosis factor-α.
To investigate which calcium channels are involved in cardiac myocyte hypertrophy induced by TNF-α, cultured cardiomyocytes were treated with 100 μg/L TNF-α. In addition, three different calcium channel blockers (2-APB, ryanodine and nifedipine) were used, and the effects of each calcium channel blocker on cardiac hypertrophy induced by TNF-α were carefully observed. Measurements included cytosolic calcium transients ([Ca2+]i), the level of intracellular calcium in individual cells, cell protein content, cell protein synthesis and cell volume. We found that the IP3R inhibitor (2-APB) and RyR inhibitor (ryanodine) both had significant suppressive effects on the level of [Ca2+]i, calcium concentration, cell protein content, cell protein synthesis and cell volume of cardiomyocytes treated with TNF-α (P<0.01). Moreover, their combined effects were significantly enhanced compared with their single effects (P<0.01). However, the inhibitor of the L type Ca2+channel nifedipine exhibited no significant suppressive effects on the increase in [Ca2+]i, calcium concentration, cell protein content, cell protein synthesis and cell volume of cardiomyocytes induced by TNF-α (P>0.05). Our results suggest that TNF-α probably induces cardiac myocyte hypertrophy by activating IP3R and RyR calcium channels, which control the release of calcium ions from the sarcoplasmic reticulum (SR) in cardiomyocytes. On the other hand, extracellular calcium influx, which is mainly regulated by the L type Ca2+channel, may not be involved in cardiac myocyte hypertrophy induced by TNF-α.
The First Affiliated Hospital, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Gui-Jun
GJ
Wang
The First Affiliated Hospital, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Lian-Yi
LY
Guo
Department of Pharmacology, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Hong-Xin
HX
Wang
The Third Affiliated Hospital, Jinzhou Medical University Jinzhou 121000, Liaoning, China.
Yu-Sheng
YS
Yao
4; 5-triphosphate receptor (IP3R); Cardiac myocyte hypertrophy; calcium; calcium channel; inositol 1; ryanodine receptor (RyR); tumor necrosis factor-α