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(Circulation Research. 2000;86:e55.)
© 2000 American Heart Association, Inc.

UltraRapid Communications

Possible Mechanism(s) of Arachidonic Acid–Induced Intracellular Acidosis in Rat Cardiac Myocytes

Mei-Lin Wu, Chih-Chiang Chan, Ming-Ja Su

From the Institutes of Physiology (M.-L.W., C.-C.C.) and Pharmacology (M.-J.S.), College of Medicine, National Taiwan University, Taipei, Taiwan.

Correspondence to Drs Mei-Lin Wu and Ming-Ja Su, Institutes of Physiology and Pharmacology, College of Medicine, National Taiwan University, No. 1, Sec. 1, Jen-Ai Rd, Taipei, Taiwan.

Abstract—Arachidonic acid (AA) and other nonesterified fatty acids (FAs) have been shown to exert harmful effects during cardiac ischemia. By continuously measuring intracellular pH (pH_i) changes in neonatal and adult cardiac myocytes, we have found, for the first time, that 10 µmol/L AA induces a substantial intracellular acidosis (0.3 to 0.4 pH units). We have ruled out the possibilities that the AA-induced acidosis is caused by (1) inhibition or stimulation of the pH_i regulators, (2) protein kinase C activation or the generation of AA metabolites or free radicals, or (3) activation of NADPH oxidase or an inward H⁺ current. The AA-induced acidosis fits to a simple diffusion mechanism, as proposed by Kamp and Hamilton (flip-flop model) for artificial phospholipid bilayers. The important properties found in the cardiac myocyte are that (1) the initial rate of acid flux (J_H) increases with the AA concentration (2 to 50 µmol/L), (2) FAs with a ^-COOH group (eg, AA, oleic acid, and linoleic acid) induce intracellular acidification, but FAs with a ^-COOCH₃ group (eg, AA methyl ester) have little effect on the pH_i, (3) tetradecylamine (FA amine) induces intracellular alkalosis, and, most importantly, (4) both the AA- and tetradecylamine-induced pH_i changes can be reversed by 0.3% BSA. Because a low concentration of AA (10 µmol/L) can induce a substantial acidosis, the possible involvement of the FA-evoked acidosis in the negative inotropic effect during cardiac ischemia is discussed. The full text of this article is available at http://www.circresaha.org.

Key Words: arachidonic acid • intracellular acidosis • ventricular myocytes

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