AJP - Heart Fuel your research with LabChart
HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
QUICK SEARCH:   [advanced]


     

Am J Physiol Heart Circ Physiol 280: H2203-H2213, 2001;
0363-6135/01 $5.00
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Alert me if a correction is posted
Right arrow Citation Map
Services
Right arrow Email this article to a friend
Right arrow Similar articles in this journal
Right arrow Similar articles in ISI Web of Science
Right arrow Similar articles in PubMed
Right arrow Alert me to new issues of the journal
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via ISI Web of Science (17)
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Korge, P.
Right arrow Articles by Weiss, J. N.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Korge, P.
Right arrow Articles by Weiss, J. N.
Vol. 280, Issue 5, H2203-H2213, May 2001

Phenylarsine oxide induces mitochondrial permeability transition, hypercontracture, and cardiac cell death

Paavo Korge, Joshua I. Goldhaber, and James N. Weiss

Cardiovascular Research Laboratory, Departments of Medicine (Cardiology) and Physiology, University of California at Los Angeles School of Medicine, Los Angeles, California 90095-1760

The mitochondrial permeability transition (MPT) is implicated in cardiac reperfusion/reoxygenation injury. In isolated ventricular myocytes, the sulfhydryl (SH) group modifier and MPT inducer phenylarsine oxide (PAO) caused MPT, severe hypercontracture, and irreversible membrane injury associated with increased cytoplasmic free [Ca2+]. Removal of extracellular Ca2+ or depletion of nonmitochondrial Ca2+ pools did not prevent these effects, whereas the MPT inhibitor cyclosporin A was partially protective and the SH-reducing agent dithiothreitol fully protective. In permeabilized myocytes, PAO caused hypercontracture at much lower free [Ca2+] than in its absence. Thus PAO induced hypercontracture by both increasing myofibrillar Ca2+ sensitivity and promoting mitochondrial Ca2+ efflux during MPT. Hypercontracture did not directly cause irreversible membrane injury because lactate dehydrogenase (LDH) release was not prevented by abolishing hypercontracture with 2,3-butanedione monoxime. However, loading myocytes with the membrane-permeable Ca2+ chelator 1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid-acetoxymethyl ester (BAPTA-AM) prevented PAO-induced LDH release, thus implicating the PAO-induced rise in cytoplasmic [Ca2+] as obligatory for irreversible membrane injury. In conclusion, PAO induces MPT and enhanced susceptibility to hypercontracture in isolated cardiac myocytes, both key features also implicated in cardiac reperfusion and reoxygenation injury.

dithiothreitol; myofibrillar Ca2+ sensitivity; mitochondrial Ca2+ efflux


This article has been cited by other articles:


Home page
 Am. J. Physiol. Heart Circ. Physiol.Home page
T. Toda, T. Kadono, M. Hoshiai, Y. Eguchi, S. Nakazawa, H. Nakazawa, N. Higashijima, and H. Ishida
Na+/H+ exchanger inhibitor cariporide attenuates the mitochondrial Ca2+ overload and PTP opening
Am J Physiol Heart Circ Physiol, December 1, 2007; 293(6): H3517 - H3523.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
K. Tanonaka, T. Iwai, K. Motegi, and S. Takeo
Effects of N-(2-mercaptopropionyl)-glycine on mitochondrial function in ischemic-reperfused heart
Cardiovasc Res, February 1, 2003; 57(2): 416 - 425.
[Abstract] [Full Text] [PDF]

Home page
 Cardiovasc ResHome page
D. J Hausenloy, H. L Maddock, G. F Baxter, and D. M Yellon
Inhibiting mitochondrial permeability transition pore opening: a new paradigm for myocardial preconditioning?
Cardiovasc Res, August 15, 2002; 55(3): 534 - 543.
[Abstract] [Full Text] [PDF]


HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS
Visit Other APS Journals Online