Details

Autor(en) / Beteiligte

• Li, Xiao-Qiang
• Zhao, Ming-Gao
• Mei, Qi-Bing
• Zhang, Yan-Feng
• Guo, Wei
• Wang, Hai-Fang
• Chen, Dan
• Cui, Yi

Titel

Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes

Ist Teil von

• Acta pharmacologica Sinica, 2003-12, Vol.24 (12), p.1224-1230

Ort / Verlag

United States

Erscheinungsjahr

2003

Quelle

MEDLINE

Beschreibungen/Notizen

• To study the effects of tumor necrosis factor-alpha (TNF-alpha) on calcium movement in rat ventricular myocytes. Intracellular free Ca2+ concentration was measured with calcium fluorescent probe Fluo-3/AM and laser confocal microscope. L-type calcium current (ICa,L) was recorded with the whole-cell configuration of the patch-clamp techniques. At 2, 20 and 200 microg/L, TNF-alpha was found to increase intracellular free Ca2+ concentration in a dose-dependent manner illustrated by the increment of calcium fluorescence density with laser confocal microscope. Nicardipine 0.5 micromol/L slightly attenuated TNF-alpha-induced response. When the cardiac myocytes were exposed to caffeine (100 mmol/L) for 30 min, TNF-alpha failed to induce any change of intracellular free calcium. However, it was found that TNF-alpha inhibited I(Ca,L) in whole-cell patch-clamp experiments. At 2, 20, and 200 microg/L, TNF-alpha decreased peak I(Ca,L) by 3.9 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.9 pA/pF+/-0.2 pA/pF, n=9, P>0.05), 15.7 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.3 pA/pF+/-0.3 pA/pF, n=9, P<0.05) and 19.6 % (-5.1 pA/pF+/-0.3 pA/pF vs -4.1 pA/pF+/-0.4 pA/pF, n=9, P<0.01), respectively. It shifted the steady-state inactivation curve of I(Ca,L) to the left (V1/2 shifted from -28.7 mV+/-0.3 mV to -37.8 mV+/-1.4 mV, n=7, P<0.05), while it took no effects on steady-state activation and recovery from inactivation. TNF-alpha inhibited I(Ca,L) in rat ventricular myocytes, while increasing the intercellular free Ca2+ level due to the release of Ca2+ from intracellular stores.