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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, November 28, 2007, 27(48):13065-13073; doi:10.1523/JNEUROSCI.3467-07.2007

This Article Full Text Full Text (PDF) Supplemental Data 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 Related articles in J. Neurosci. Similar articles in this journal Similar articles in 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 Web of Science (8) Citing Articles via Google Scholar Google Scholar Articles by Ifuku, M. Articles by Noda, M. Search for Related Content PubMed PubMed Citation Articles by Ifuku, M. Articles by Noda, M.

 Previous Article  |  Next Article 

Cellular/Molecular
Bradykinin-Induced Microglial Migration Mediated by B₁-Bradykinin Receptors Depends on Ca²⁺ Influx via Reverse-Mode Activity of the Na⁺/Ca²⁺ Exchanger

Masataka Ifuku,¹ Katrin Färber,² Yuko Okuno,¹ Yukiko Yamakawa,¹ Taiki Miyamoto,¹ Christiane Nolte,² Vanessa F. Merrino,² Satomi Kita,³ Takahiro Iwamoto,³ Issei Komuro,⁴ Bing Wang,¹ Giselle Cheung,² Eiichi Ishikawa,⁵ Hiroaki Ooboshi,⁵ Michael Bader,² Keiji Wada,⁶ Helmut Kettenmann,² and Mami Noda¹

¹Laboratory of Pathophysiology, Graduate School of Pharmaceutical Science, Kyushu University, Fukuoka 812-8582, Japan, ²Max-Delbrück-Center for Molecular Medicine, 13125 Berlin, Germany, ³Department of Pharmacology, School of Medicine, Fukuoka University, Fukuoka 812-0180, Japan, ⁴Department of Cardiovascular Science and Medicine, Chiba University Graduate School of Medicine, Chuo-ku, Chiba 260-8670, Japan, ⁵Department of Medicine and Clinical Science, Graduate School of Medical Sciences, Kyushu University, Fukuoka 814-0180, Japan, and ⁶Department of Degenerative Neurological Diseases, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Tokyo 187-8502, Japan

Correspondence should be addressed to Dr. Mami Noda, Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Email: noda{at}phar.kyushu-u.ac.jp

Bradykinin (BK) is produced and acts at the site of injury and inflammation. In the CNS, migration of microglia toward the lesion site plays an important role pathologically. In the present study, we investigated the effect of BK on microglial migration. Increased motility of cultured microglia was mimicked by B₁ receptor agonists and markedly inhibited by a B₁ antagonist_, but not by a B₂ receptor antagonist. BK induced chemotaxis in microglia isolated from wild-type and B₂-knock-out mice but not from B₁-knock-out mice. BK-induced motility was not blocked by pertussis toxin but was blocked by chelating intracellular Ca²⁺ or by low extracellular Ca²⁺, implying that Ca²⁺ influx is prerequisite. Blocking the reverse mode of Na⁺/Ca²⁺ exchanger (NCX) completely inhibited BK-induced migration. The involvement of NCX was further confirmed by using NCX^+/– mice; B₁-agonist-induced motility and chemotaxis was decreased compared with that in NCX^+/+ mice. Activation of NCX seemed to be dependent on protein kinase C and phosphoinositide 3-kinase, and resultant activation of intermediate-conductance (IK-type) Ca²⁺-dependent K⁺ currents (I_K(Ca)) was activated. Despite these effects, BK did not activate microglia, as judged from OX6 staining. Using in vivo lesion models and pharmacological injection to the brain, it was shown that microglial accumulation around the lesion was also dependent on B₁ receptors and I_K(Ca). These observations support the view that BK functions as a chemoattractant by using the distinct signal pathways in the brain and, thus, attracts microglia to the lesion site in vivo.

Key words: microglia; bradykinin; Na⁺/Ca²⁺ exchanger; Ca²⁺-dependent K⁺ current; chemotaxis; motility

---

Received Dec. 29, 2006; revised Sept. 12, 2006; accepted Sept. 20, 2007.

Correspondence should be addressed to Dr. Mami Noda, Laboratory of Pathophysiology, Graduate School of Pharmaceutical Sciences, Kyushu University, Fukuoka 812-8582, Japan. Email: noda{at}phar.kyushu-u.ac.jp

Related articles in J. Neurosci.:

Bradykinin: A Microglia Attractant In Vivo?

Christian Huisman, Peter Kok, Lianne Schmaal, and Pim Verhoog
J. Neurosci. 2008 28: 3531-3532. [Full Text]  

This article has been cited by other articles:

				K. Sakamoto, Y. Owada, Y. Shikama, I. Wada, S. Waguri, T. Iwamoto, and J. Kimura Involvement of Na+/Ca2+ exchanger in migration and contraction of rat cultured tendon fibroblasts J. Physiol., November 15, 2009; 587(22): 5345 - 5359. [Abstract] [Full Text] [PDF]

				F. Boscia, R. Gala, A. Pannaccione, A. Secondo, A. Scorziello, G. Di Renzo, and L. Annunziato NCX1 Expression and Functional Activity Increase in Microglia Invading the Infarct Core Stroke, November 1, 2009; 40(11): 3608 - 3617. [Abstract] [Full Text] [PDF]

				X.-p. Tong, X.-y. Li, B. Zhou, W. Shen, Z.-j. Zhang, T.-l. Xu, and S. Duan Ca2+ signaling evoked by activation of Na+ channels and Na+/Ca2+ exchangers is required for GABA-induced NG2 cell migration J. Cell Biol., July 13, 2009; 186(1): 113 - 128. [Abstract] [Full Text] [PDF]

				M. Zhang, X.-W. Fei, Y.-L. He, G. Yang, and Y.-A. Mei Bradykinin inhibits the transient outward K+ current in mouse Schwann cells via the cAMP/PKA pathway Am J Physiol Cell Physiol, June 1, 2009; 296(6): C1364 - C1372. [Abstract] [Full Text] [PDF]

				C. Huisman, P. Kok, L. Schmaal, and P. Verhoog Bradykinin: A Microglia Attractant In Vivo? J. Neurosci., April 2, 2008; 28(14): 3531 - 3532. [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help