DOI: 10.1152/ajpcell.2001.281.4.c1146. Acute inhibition of brain-specific Na<sup>+</sup>/H<sup>+</sup> exchanger isoform 5 by protein kinases A and C and cell shrinkage

Acute inhibition of brain-specific Na+/H+ exchanger isoform 5 by protein kinases A and C and cell shrinkage

10.1152/ajpcell.2001.281.4.c1146

Crossref journal-article

American Physiological Society

American Journal of Physiology-Cell Physiology (24)

Abstract

Little is known of the functional properties of the mammalian, brain-specific Na+/H+ exchanger isoform 5 (NHE5). Rat NHE5 was stably expressed in NHE-deficient PS120 cells, and its activity was characterized using the fluorescent pH-sensitive dye 2′,7′-bis(2-carboxyethyl)-5(6)-carboxyfluorescein. NHE5 was insensitive to ethylisopropyl amiloride. The transport kinetics displayed a simple Michaelis-Menten relationship for extracellular Na+ (apparent K Na= 27 ± 5 mM) and a Hill coefficient near 3 for the intracellular proton concentration with a half-maximal activity at an intracellular pH of 6.93 ± 0.03. NHE5 activity was inhibited by acute exposure to 8-bromo-cAMP or forskolin (which increases intracellular cAMP by activating adenylate cyclase). The kinase inhibitor H-89 reversed this inhibition, suggesting that regulation by cAMP involves a protein kinase A (PKA)-dependent process. In contrast, 8-bromo-cGMP did not have a significant effect on activity. The protein kinase C (PKC) activator phorbol 12-myristrate 13-acetate inhibited NHE5, and the PKC antagonist chelerythrine chloride blunted this effect. Activity was also inhibited by hyperosmotic-induced cell shrinkage but was unaffected by a hyposmotic challenge. These results demonstrate that rat brain NHE5 is downregulated by activation of PKA and PKC and by cell shrinkage, important regulators of neuronal cell function.

Bibliography

Attaphitaya, S., Nehrke, K., & Melvin, J. E. (2001). Acute inhibition of brain-specific Na+/H+ exchanger isoform 5 by protein kinases A and C and cell shrinkage. American Journal of Physiology-Cell Physiology, 281(4), C1146âC1157.

Authors 3

Surat Attaphitaya (first)
Keith Nehrke (additional)
James E. Melvin (additional)

References 53 Referenced 25

Dates

Type	When
Created	7 years, 8 months ago (Dec. 24, 2017, 3:40 p.m.)
Deposited	1 year, 2 months ago (June 17, 2024, 3:16 p.m.)
Indexed	4 months, 1 week ago (April 22, 2025, 2:28 a.m.)
Issued	23 years, 10 months ago (Oct. 1, 2001)
Published	23 years, 10 months ago (Oct. 1, 2001)
Published Print	23 years, 10 months ago (Oct. 1, 2001)

Funders 0

None

BibTeX

@article{Attaphitaya_2001, title={Acute inhibition of brain-specific Na+/H+ exchanger isoform 5 by protein kinases A and C and cell shrinkage}, volume={281}, ISSN={1522-1563}, url={http://dx.doi.org/10.1152/ajpcell.2001.281.4.c1146}, DOI={10.1152/ajpcell.2001.281.4.c1146}, number={4}, journal={American Journal of Physiology-Cell Physiology}, publisher={American Physiological Society}, author={Attaphitaya, Surat and Nehrke, Keith and Melvin, James E.}, year={2001}, month=oct, pages={C1146–C1157} }

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