TNF alpha inhibited cardiac L-type Ca2+ channel current and contractile Ca2+ transients in rat cardiac myocytes, suggesting its negative inotropic effects are mediated by TNFRI.
Does TNF alpha inhibit L-type Ca2+ current and Ca2+ transients in rat cardiac myocytes?
The cardiotoxic and negative inotropic effects of TNF alpha may be mediated by TNFRI blockade of cardiac excitation-contraction coupling.
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, 125ITNF 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.
Krown et al. (Mon,) reported a other. TNF alpha was evaluated on L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. TNF alpha inhibited cardiac L-type Ca2+ channel current and contractile Ca2+ transients in rat cardiac myocytes, suggesting its negative inotropic effects are mediated by TNFRI.