Muscimol Directly Activates the TREK-2 Channel Expressed in GABAergic Neurons through Its N-Terminusopen access
- Kim, Eun-Jin; Kwon, Oh-Sang; Hur, Chang-Gi; Nyiramana, Marie Merci; Lee, Dong-Kun; Hong, Seong-Geun; Han, Jaehee; Kang, Dawon
- Issue Date
- gamma-aminobutyric acid; gamma-aminobutyric acid receptor; two-pore domain K+ channel
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, v.22, no.17
- Journal Title
- INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
- The two-pore domain K+ (K-2P) channel, which is involved in setting the resting membrane potential in neurons, is an essential target for receptor agonists. Activation of the gamma-aminobutyric acid (GABA) receptors (GABA(A)R and GABA(B)R) reduces cellular excitability through Cl- influx and K+ efflux in neurons. Relatively little is known about the link between GABA(A)R and the K+ channel. The present study was performed to identify the effect of GABAR agonists on K-2P channel expression and activity in the neuroblastic B35 cells that maintain glutamic acid decarboxylase (GAD) activity and express GABA. TASK and TREK/TRAAK mRNA were expressed in B35 cells with a high level of TREK-2 and TRAAK. In addition, TREK/TRAAK proteins were detected in the GABAergic neurons obtained from GABA transgenic mice. Furthermore, TREK-2 mRNA and protein expression levels were markedly upregulated in B35 cells by GABA(A)R and GABA(B)R agonists. In particular, muscimol, a GABA(A)R agonist, significantly increased TREK-2 expression and activity, but the effect was reduced in the presence of the GABA(A)R antagonist bicuculine or TREK-2 inhibitor norfluoxetine. In the whole-cell and single-channel patch configurations, muscimol increased TREK-2 activity, but the muscimol effect disappeared in the N-terminal deletion mutant. These results indicate that muscimol directly induces TREK-2 activation through the N-terminus and suggest that muscimol can reduce cellular excitability by activating the TREK-2 channel and by inducing Cl- influx in GABAergic neurons.
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- College of Medicine > Department of Medicine > Journal Articles
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