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

doi:10.1016/0014-5793(95)01238-5

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 journal › Article › peer-review

122 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 (I_Ca) 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 language	English (US)
Pages (from-to)	24-30
Number of pages	7
Journal	FEBS Letters
Volume	376
Issue number	1-2
DOIs	https://doi.org/10.1016/0014-5793(95)01238-5
State	Published - Nov 27 1995
Externally published	Yes

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

Access to Document

10.1016/0014-5793(95)01238-5

Cite this

@article{50bd336369b14ec78da6a9bb7547c227,

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

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.",

keywords = "Cardiac Ca, Inotropy, Rat cardiac myocyte, Single cell RT-PCR, TNFα receptor",

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

note = "Funding Information: Acknowledgements: The authors gratefully acknowledge Sue Murray and Donna Thuerauf for help with DNA sequencing and RT-PCR. We also acknowledge the advice of Dr. Diane K. O'Dowd on the single cell RT-PCR work. Supported by grants from the American Heart Association National Center (#941459, Dr. Sabbadini), the Muscular Dystrophy Assoc. Inc. (Dr. Sabbadini), the National Institutes of Health (#HL42527, Dr. Palade and #1RO3 DC02579-0A1, Dr. Dubin), the American Heart Association California Affiliate (#92-275, Dr. Harris), and the Whitehall Foundation (J94-11, Dr. Dubin).",

year = "1995",

month = nov,

day = "27",

doi = "10.1016/0014-5793(95)01238-5",

language = "English (US)",

volume = "376",

pages = "24--30",

journal = "FEBS Letters",

issn = "0014-5793",

publisher = "John Wiley and Sons Inc.",

number = "1-2",

}

TY - JOUR

T1 - TNFα receptor expression in rat cardiac myocytes

T2 - TNFα inhibition of L-type Ca2+ current and Ca2+ transients

AU - Krown, Kevin A.

AU - Yasui, Kenji

AU - Brooker, Madelyne J.

AU - Dubin, Adrienne E.

AU - Nguyen, Cuong

AU - Harris, Greg L.

AU - McDonough, Patrick M.

AU - Glembotski, Christopher C.

AU - Palade, Philip T.

AU - Sabbadini, Roger A.

N1 - Funding Information: Acknowledgements: The authors gratefully acknowledge Sue Murray and Donna Thuerauf for help with DNA sequencing and RT-PCR. We also acknowledge the advice of Dr. Diane K. O'Dowd on the single cell RT-PCR work. Supported by grants from the American Heart Association National Center (#941459, Dr. Sabbadini), the Muscular Dystrophy Assoc. Inc. (Dr. Sabbadini), the National Institutes of Health (#HL42527, Dr. Palade and #1RO3 DC02579-0A1, Dr. Dubin), the American Heart Association California Affiliate (#92-275, Dr. Harris), and the Whitehall Foundation (J94-11, Dr. Dubin).

PY - 1995/11/27

Y1 - 1995/11/27

N2 - 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.

AB - 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.

KW - Cardiac Ca

KW - Inotropy

KW - Rat cardiac myocyte

KW - Single cell RT-PCR

KW - TNFα receptor

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