Related Experiment Video
Updated: Sep 29, 2026
Primary Culture of Adult Rat Heart Myocytes
Published on: June 16, 2009
TNF alpha receptor expression in rat cardiac myocytes: TNF alpha inhibition of L-type Ca2+ current and Ca2+
K A Krown1, K Yasui, M J Brooker
1Department of Biology, San Diego State University, CA 92182, USA.
Abstract:
Tumor necrosis factor-alpha (TNF alpha) is a potentially powerful anti-neoplastic agent; however, its therapeutic usefulness is limited by its cardiotoxic and negative inotropic effects. Accordingly, studies were undertaken to gain a better understanding of the mechanisms of TNF alpha-mediated cardiodepression. Single cell RT-PCR, [125I]TNF alpha ligand binding and Western immunoblotting experiments demonstrated that rat cardiac cells predominantly express type I TNF alpha receptors (TNFRI or p60). TNF alpha inhibited cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. Thus, it is possible that the negative inotropic effects of TNF alpha are the result of TNFRI-mediated blockade of cardiac excitation-contraction coupling.
Insights
Tumor necrosis factor-alpha (TNF alpha) limits cancer therapy due to heart toxicity. This study reveals TNF alpha blocks cardiac calcium channels via TNFRI, explaining its negative inotropic effects.
Area of Science:
- Cardiology
- Molecular Biology
- Pharmacology
Background:
- Tumor necrosis factor-alpha (TNF alpha) shows anti-cancer potential but causes cardiotoxicity.
- Understanding TNF alpha's cardiac effects is crucial for its therapeutic application.
Purpose of the Study:
- To investigate the mechanisms underlying TNF alpha-induced cardiodepression.
- To determine the role of TNF alpha receptors in cardiac function.
Main Methods:
- Single cell RT-PCR to identify receptor expression in cardiac cells.
- [125I]TNF alpha ligand binding assays.
- Western immunoblotting to confirm receptor presence.
- Measurement of cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients.
Main Results:
- Rat cardiac cells predominantly express type I TNF alpha receptors (TNFRI or p60).
- TNF alpha significantly inhibited cardiac L-type Ca2+ channel current (ICa).
- TNF alpha reduced contractile Ca2+ transients in cardiac cells.
Conclusions:
- TNF alpha-mediated cardiodepression may result from TNFRI signaling.
- TNFRI blockade of cardiac excitation-contraction coupling is a likely mechanism.
- These findings offer insights into managing TNF alpha's cardiotoxic side effects.
