Although tight regulation of intracellular pH (pHi) is critical for the survival under stress, paradoxically a slowed recovery of pHi under hypoxic injury may be cardioprotective. In this study, we investigated the recovery of pHi after hypoxia-induced intracellular acidosis in cardiomyocytes loaded with the H+-sensitive dye SNARF-1. Exposure of single cardiomyocytes to 2,4-dinitrophenol (DNP), an inhibitor of mitochondrial oxidative phosphorylation, induced significant intracellular acidification. However, within 10–12 min upon removal of DNP, cardiomyocytes restituted their intracellular H+ concentration. The presence either of 5-N-ethyl-N-isopropylamiloride (EIPA) an inhibitor of Na/H antiporter, or 4,4′-diisothiocyanatostilbene-2,2′-disulfonic acid (DIDS), an inhibitor of bicarbonate-dependent exchange, did not modify the cellular response to DNP. But, combined use of EIPA and DIDS prevented the restitution of intracellular pH following removal of DNP. This study, thus, demonstrated, for the first time, that blockade of both Na/H and bicarbonate-dependent exchange is necessary and sufficient to maintain the hypoxia-induced intracellular acidification. Therefore, concomitant blockade of both pH-regulating mechanisms deserves to be further considered as a novel strategy against hypoxia-reoxygenation injury in the heart.
Skip Nav Destination
Article navigation
Research Article|
April 01 1999
Inhibition of Both Na/H and Bicarbonate-Dependent Exchange is Required to Prevent Recovery of Intracellular pH in Single Cardiomyocytes Exposed to Metabolic Stress
Oscar K. Serrano;
Oscar K. Serrano
1Division of Cardiovascular Diseases, Department of Medicine Mayo Clinic, Mayo Foundation, Rochester, MN, 55905
Search for other works by this author on:
Aleksandar Jovanovic;
Aleksandar Jovanovic
1Division of Cardiovascular Diseases, Department of Medicine Mayo Clinic, Mayo Foundation, Rochester, MN, 55905
Search for other works by this author on:
Andre Terzic
Andre Terzic
1Division of Cardiovascular Diseases, Department of Medicine Mayo Clinic, Mayo Foundation, Rochester, MN, 55905
Search for other works by this author on:
Publisher: Portland Press Ltd
Online ISSN: 1573-4935
Print ISSN: 0144-8463
© 1999 Plenum Publishing Corporation
1999
Biosci Rep (1999) 19 (2): 99–107.
Citation
Oscar K. Serrano, Aleksandar Jovanovic, Andre Terzic; Inhibition of Both Na/H and Bicarbonate-Dependent Exchange is Required to Prevent Recovery of Intracellular pH in Single Cardiomyocytes Exposed to Metabolic Stress. Biosci Rep 1 April 1999; 19 (2): 99–107. doi: https://doi.org/10.1023/A:1020158426538
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |