TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation.

Dong Ho Woo, Kyung Seok Han, Jae Wan Shim, Bo Eun Yoon, Eunju Kim, Jin Young Bae, Soo Jin Oh, Eun Mi Hwang, Alan D Marmorstein, Yong Chul Bae, Jae Yong Park, C. Justin Lee

Research output: Contribution to journalArticle

150 Citations (Scopus)

Abstract

Astrocytes release glutamate upon activation of various GPCRs to exert important roles in synaptic functions. However, the molecular mechanism of release has been controversial. Here, we report two kinetically distinct modes of nonvesicular, channel-mediated glutamate release. The fast mode requires activation of G(αi), dissociation of G(βγ), and subsequent opening of glutamate-permeable, two-pore domain potassium channel TREK-1 through direct interaction between G(βγ) and N terminus of TREK-1. The slow mode is Ca(2+) dependent and requires G(αq) activation and opening of glutamate-permeable, Ca(2+)-activated anion channel Best1. Ultrastructural analyses demonstrate that TREK-1 is preferentially localized at cell body and processes, whereas Best1 is mostly found in microdomains of astrocytes near synapses. Diffusion modeling predicts that the fast mode can target neuronal mGluR with peak glutamate concentration of 100 μM, whereas slow mode targets neuronal NMDA receptors at around 1 μM. Our results reveal two distinct sources of astrocytic glutamate that can differentially influence neighboring neurons.

Original languageEnglish (US)
Pages (from-to)25-40
Number of pages16
JournalCell
Volume151
Issue number1
StatePublished - Sep 28 2012
Externally publishedYes

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Astrocytes
Glutamic Acid
Chemical activation
N-Methyl-D-Aspartate Receptors
Synapses
Neurons
Anions
potassium channel protein TREK-1
Cells

ASJC Scopus subject areas

  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

Woo, D. H., Han, K. S., Shim, J. W., Yoon, B. E., Kim, E., Bae, J. Y., ... Lee, C. J. (2012). TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell, 151(1), 25-40.

TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. / Woo, Dong Ho; Han, Kyung Seok; Shim, Jae Wan; Yoon, Bo Eun; Kim, Eunju; Bae, Jin Young; Oh, Soo Jin; Hwang, Eun Mi; Marmorstein, Alan D; Bae, Yong Chul; Park, Jae Yong; Lee, C. Justin.

In: Cell, Vol. 151, No. 1, 28.09.2012, p. 25-40.

Research output: Contribution to journalArticle

Woo, DH, Han, KS, Shim, JW, Yoon, BE, Kim, E, Bae, JY, Oh, SJ, Hwang, EM, Marmorstein, AD, Bae, YC, Park, JY & Lee, CJ 2012, 'TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation.', Cell, vol. 151, no. 1, pp. 25-40.
Woo DH, Han KS, Shim JW, Yoon BE, Kim E, Bae JY et al. TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. Cell. 2012 Sep 28;151(1):25-40.
Woo, Dong Ho ; Han, Kyung Seok ; Shim, Jae Wan ; Yoon, Bo Eun ; Kim, Eunju ; Bae, Jin Young ; Oh, Soo Jin ; Hwang, Eun Mi ; Marmorstein, Alan D ; Bae, Yong Chul ; Park, Jae Yong ; Lee, C. Justin. / TREK-1 and Best1 channels mediate fast and slow glutamate release in astrocytes upon GPCR activation. In: Cell. 2012 ; Vol. 151, No. 1. pp. 25-40.
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