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

124 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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