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首页> 外文期刊>Journal of Neurophysiology >Diurnal properties of tonic and synaptic GABA(A) receptor-mediated currents in suprachiasmatic nucleus neurons
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Diurnal properties of tonic and synaptic GABA(A) receptor-mediated currents in suprachiasmatic nucleus neurons

机译：Diurnal properties of tonic and synaptic GABA(A) receptor-mediated currents in suprachiasmatic nucleus neurons

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摘要

Synaptic and extrasynaptic GABA(A) receptor (GABA(A)R)-mediated neurotransmission is a critical component of the suprachiasmatic nucleus (SCN) neuronal network. However, the properties of the GABA(A) tonic current (I-tonic) and its origin remain unexplored. Spontaneous GABA(A) postsynaptic currents (sGPSCs) and I-tonic were recorded from SCN neurons with the whole cell voltage-clamp technique at different times of the day. GABA(A)R antagonists (bicuculline, gabazine, and picrotoxin) inhibited sGPSC and induced an outward shift of the holding current, which defined the I-tonic amplitude. The sGPSC frequency, synaptic charge transfer, and I-tonic amplitude all demonstrated significant diurnal rhythms, with peaks in the middle of the day [zeitgeber time (ZT)7-8] and nadirs at night (ZT19-20). The I-tonic amplitude increased proportionally with the sGPSC frequency and synaptic charge transfer during the day and required action potential-mediated GABA release, which was confirmed by TTX application. The activation of presynaptic GABA(B) receptors by baclofen did not significantly alter the I-tonic of neurons with low-frequency sGPSC. The equilibrium potential (Eq) for I-tonic was similar to the Eq for chloride and GABA(A) receptor-activated currents. I-tonic showed outward rectification at membrane potentials over the range of -70 to -10 mV and then was linear at voltages greater than -10 mV. GABA(A)R containing alpha 4-, alpha 5-, and delta-subunits were expressed in SCN, and their contribution to I-tonic was confirmed by application of the GABA(A)R agonist 4,5,6,7-tetrahydroisoxazolo[5,4-c]pyridin-3-ol (THIP) and the GABA(A)R inverse agonist 11,12,13,13a-tetrahydro-7-methoxy-9-oxo-9H-imidazo[1,5-a]pyrrolo[2,1-c][1,4]benzodiazepine-1-carboxylic acid ethyl ester (L655,708). Thus, the I-tonic was mediated by extrasynaptic GABA(A)Rs activated predominantly by GABA diffusing out of GABAergic synapses.

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