TNFα receptor expression in rat cardiac myocytes: TNFα inhibition of L-type Ca2+ current and Ca2+ transients

Kevin A. Krown, Kenji Yasui, Madelyne J. Brooker, Adrienne E. Dubin, Cuong Nguyen, Greg L. Harris, Patrick M. McDonough, Christopher C. Glembotski, Philip T. Palade, Roger A. Sabbadini

Research output: Contribution to journalArticlepeer-review

120 Scopus citations

Abstract

Tumor necrosis factor-α (TNFα) 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 TNFα-mediated cardiodepression. Single cell RT-PCR, [125I]TNFα ligand binding and Western immunoblotting experiments demonstrated that rat cardiac cells predominantly express type I TNFα receptors (TNFRI or p60). TNFα inhibited cardiac L-type Ca2+ channel current (ICa) and contractile Ca2+ transients. Thus, it is possible that the negative inotropic effects of TNFα are the result of TNFRI-mediated blockade of cardiac excitation-contraction coupling.

Original languageEnglish (US)
Pages (from-to)24-30
Number of pages7
JournalFEBS Letters
Volume376
Issue number1-2
DOIs
StatePublished - Nov 27 1995
Externally publishedYes

Keywords

  • Cardiac Ca
  • Inotropy
  • Rat cardiac myocyte
  • Single cell RT-PCR
  • TNFα receptor

ASJC Scopus subject areas

  • Biophysics
  • Structural Biology
  • Biochemistry
  • Molecular Biology
  • Genetics
  • Cell Biology

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