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, [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.
Department of Biology, San Diego State University, CA 92182, USA.
K A
KA
Krown
K
K
Yasui
M J
MJ
Brooker
A E
AE
Dubin
C
C
Nguyen
G L
GL
Harris
P M
PM
McDonough
C C
CC
Glembotski
P T
PT
Palade
R A
RA
Sabbadini
D000818:Animals; D001483:Base Sequence; D002118:Calcium / Q000037:antagonists & inhibitors / Q000378:metabolism; D015220:Calcium Channels / Q000378:metabolism; D017931:DNA Primers / Q000737:chemistry; D005456:Fluorescent Dyes / Q000378:metabolism; D015870:Gene Expression / Q000235:genetics; D015151:Immunoblotting; D066298:In Vitro Techniques; D007211:Indoles / Q000378:metabolism; D008969:Molecular Sequence Data; D009206:Myocardium / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D018124:Receptors, Tumor Necrosis Factor / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D015220:Calcium Channels; D017931:DNA Primers; D005456:Fluorescent Dyes; D007211:Indoles; D012333:RNA, Messenger; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha; C048960:indo-1; D002118:Calcium