TNF-ALPHA RECEPTOR EXPRESSION IN RAT CARDIAC MYOCYTES - TNF-ALPHA INHIBITION OF L-TYPE CA2+ CURRENT AND CA2+ TRANSIENTS

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, [I-125]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 (I-Ca) 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.