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Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes.
Acta Pharmacol Sin. 2003 Dec; 24(12):1224-30.AP

Abstract

AIM

To study the effects of tumor necrosis factor-alpha (TNF-alpha) on calcium movement in rat ventricular myocytes.

METHODS

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.

RESULTS

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.

CONCLUSION

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.

Authors+Show Affiliations

Li XQ
Department of Pharmacology, The Fourth Military Medical University, Xi-an 710032, China.
Zhao MG
No affiliation info available
Mei QB
No affiliation info available
Zhang YF
No affiliation info available
Guo W
No affiliation info available
Wang HF
No affiliation info available
Chen D
No affiliation info available
Cui Y
No affiliation info available

MeSH

AnimalsCalciumCalcium Channels, L-TypeCell SeparationHeart VentriclesMaleMyocardiumMyocytes, CardiacPatch-Clamp TechniquesRatsRats, Sprague-DawleyTumor Necrosis Factor-alpha

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

14653948

Citation

Li, Xiao-Qiang, et al. "Effects of Tumor Necrosis Factor-alpha On Calcium Movement in Rat Ventricular Myocytes." Acta Pharmacologica Sinica, vol. 24, no. 12, 2003, pp. 1224-30.
Li XQ, Zhao MG, Mei QB, et al. Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. Acta Pharmacol Sin. 2003;24(12):1224-30.
Li, X. Q., Zhao, M. G., Mei, Q. B., Zhang, Y. F., Guo, W., Wang, H. F., Chen, D., & Cui, Y. (2003). Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. Acta Pharmacologica Sinica, 24(12), 1224-30.
Li XQ, et al. Effects of Tumor Necrosis Factor-alpha On Calcium Movement in Rat Ventricular Myocytes. Acta Pharmacol Sin. 2003;24(12):1224-30. PubMed PMID: 14653948.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Effects of tumor necrosis factor-alpha on calcium movement in rat ventricular myocytes. AU - Li,Xiao-Qiang, AU - Zhao,Ming-Gao, AU - Mei,Qi-Bing, AU - Zhang,Yan-Feng, AU - Guo,Wei, AU - Wang,Hai-Fang, AU - Chen,Dan, AU - Cui,Yi, PY - 2003/12/5/pubmed PY - 2004/8/7/medline PY - 2003/12/5/entrez SP - 1224 EP - 30 JF - Acta pharmacologica Sinica JO - Acta Pharmacol Sin VL - 24 IS - 12 N2 - AIM: To study the effects of tumor necrosis factor-alpha (TNF-alpha) on calcium movement in rat ventricular myocytes. METHODS: 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. RESULTS: 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. CONCLUSION: 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. SN - 1671-4083 UR - https://www.unboundmedicine.com/medline/citation/14653948/Effects_of_tumor_necrosis_factor_alpha_on_calcium_movement_in_rat_ventricular_myocytes_ DB - PRIME DP - Unbound Medicine ER -