QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (20) Citing Articles via Google Scholar Google Scholar Articles by Morihata, H. Articles by Kuno, M. Search for Related Content PubMed PubMed Citation Articles by Morihata, H. Articles by Kuno, M. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Hazardous Substances DB CYTOCHALASIN D LACTIC ACID PHALLOIDIN ZINC CHLORIDE ZINC COMPOUNDS

 Previous Article  |  Next Article 

The Journal of Neuroscience, October 1, 2000, 20(19):7220-7227

Potentiation of a Voltage-Gated Proton Current in Acidosis-Induced Swelling of Rat Microglia

Hirokazu Morihata¹, Fusao Nakamura¹, Tsuyoshi Tsutada², and Miyuki Kuno¹

Departments of ¹ Physiology and ² Neurology, Osaka City University Medical School, Abeno-ku, Osaka 545-8585, Japan

Microglia are equipped with a strong proton (H⁺) extrusion pathway, a voltage-gated H⁺ channel, probably to compensate for the large amount of H⁺ generated during phagocytosis; however, little is known about how this channel is regulated in pathological states. Because neural damage is often associated with intracellular and extracellular acidosis, we examined the regulatory mechanisms of the H⁺ current of rat spinal microglia in acidic environments. More than 90% of round/amoeboid microglia expressed the H⁺ current, which was characterized by slow activation kinetics, dependencies on both intracellular and extracellular pH, and blockage by Zn²⁺. Extracellular lactoacidosis, pH 6.8, induced intracellular acidification and cell swelling. Cell swelling was also induced by intracellular dialysis with acidic pipette solutions, pH 5.5-6.8, at normal extracellular pH 7.3 in the presence of Na⁺. The H⁺ currents were increased in association with cell swelling as shown by shifts of the half-activation voltage to more negative potentials and by acceleration of the activation kinetics. The acidosis-induced cell swelling and the accompanying potentiation of the H⁺ current required nonhydrolytic actions of intracellular ATP and were inhibited by agents affecting actin filaments (phalloidin and cytochalasin D). The H⁺ current was also potentiated by swelling caused by hypotonic stress. These findings suggest that the H⁺ channel of microglia can be potentiated via cell swelling induced by intracellular acidification. This potentiation might operate as a negative feedback mechanism to protect microglia from cytotoxic acidification and hence acidosis-induced swelling in pathological states of the CNS.

Key words: H⁺ channel; lactoacidosis; cell swelling; microglia; pH regulation; ATP; cytochalasin D; cytoskeleton; spinal cord

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20197220-08$05.00/0

This article has been cited by other articles:

				M. Nakanishi, T. Mori, K. Nishikawa, M. Sawada, M. Kuno, and A. Asada The Effects of General Anesthetics on P2X7 and P2Y Receptors in a Rat Microglial Cell Line Anesth. Analg., May 1, 2007; 104(5): 1136 - 1144. [Abstract] [Full Text] [PDF]

				T. E. Decoursey Voltage-Gated Proton Channels and Other Proton Transfer Pathways Physiol Rev, April 1, 2003; 83(2): 475 - 579. [Abstract] [Full Text] [PDF]

				L. M. Henderson and R. W. Meech Proton Conduction through gp91phox J. Gen. Physiol., November 25, 2002; 120(6): 759 - 765. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help