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Intracellular pH regulatory mechanism in human atrial myocardium: Functional evidence for Na+/H+ exchanger and Na+/HCO −3 symporter

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Journal of Biomedical Science

Abstract

Intracellular pH (pHi) exerts considerable influence on cardiac contractility and rhythm. Over the last few years, extensive progress has been made in understanding the system that controls pHi in animal cardiomyocytes. In addition to the housekeeping Na+-H+ exchanger (NHE), the Na+-HCO −3 symporter (NHS) has been demonstrated in animal cardiomyocytes as another and extruder. However, whether the NHE and NHS functions exist in human atrial cardiomyocytes remains unclear. We therefore investigated the mechanism of pHi recovery from intracellular acidosis (induced by NH4Cl prepulse) using intracellular 2′,7′-bis(2-carboxethyl)-5(6)-carboxyfluorescein fluorescence in human atrial myocardium. In HEPES (nominally HCO −3 -free) Tyrode solution, pHi recovery from induced intracellular acidosis could be blocked completely by 30 µM 3-methylsulfonyl-4-piperidinobenzoyl, guanidine hydrochloride (HOE 694), a specific NHE inhibitor, or by removing extracellular Na+. In 3% CO2-HCO −3 Tyrode solution, HOE 694 only slowed the pHi recovery, while addition of HOE 694 together with 4,4′-diisothiocyanatostilbene-2,2′-disulphonic acid (an NHS inhibitor) or removal of extracellular Na+ inhibited the acid extrusion entirely. Therefore, in the present study, we provided evidence that two acid extruders involved in acid extrusion in human atrial myocytes, one which is HCO −3 independent and one which is HCO −3 dependent, are mostly likely NHE and NHS, respectively. When we checked the percentage of contribution of these two carriers to pHi recovery following induced acidosis, we found that the activity of NHE increased steeply in the acid direction, while that of NHS did not change. Our present data indicate for the first time that two acid extruders, NHE and NHS, exist functionally and pHi dependently in human atrial cardiomyocytes.

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Authors and Affiliations

  1. Department of Gynecology, National Defense Medical Center, Taipei, Taiwan, ROC

    Wei-Hwa Chen

  2. Department of Cardiovascular Surgery, National Defense Medical Center, Taipei, Taiwan, ROC

    Chien-Sung Tsai & Guo-Chen Lee

  3. Department of Pathology, National Defense Medical Center, Taipei, Taiwan, ROC

    Jong-Shiaw Jin

  4. Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan, ROC

    Tzu-Hurng Cheng & Jin-Jer Chen

  5. Department of Pharmacology, National Defense Medical Center, Neihu PO 90048-504, Taipei, Taiwan (ROC)

    Shih-Hurng Loh & Cheng-Hsien Chiang

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  1. Shih-Hurng Loh
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Loh, SH., Chen, WH., Chiang, CH. et al. Intracellular pH regulatory mechanism in human atrial myocardium: Functional evidence for Na+/H+ exchanger and Na+/HCO −3 symporter. J Biomed Sci 9, 198–205 (2002). https://doi.org/10.1007/BF02256066

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  • DOI: https://doi.org/10.1007/BF02256066

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