Neuroscience Graduate Program, Oregon Health & Science University, Portland, Oregon, USA.
Oregon Institute for Occupational Health Sciences, Oregon Health & Science University, Portland, Oregon, USA.
J Biol Rhythms. 2022 Feb;37(1):110-123. doi: 10.1177/07487304211059770. Epub 2022 Jan 7.
Both inhibitory and excitatory GABA transmission exist in the mature suprachiasmatic nucleus (SCN), the master pacemaker of circadian physiology. Whether GABA is inhibitory or excitatory depends on the intracellular chloride concentration ([Cl]). Here, using the genetically encoded ratiometric probe Cl-Sensor, we investigated [Cl] in AVP and VIP-expressing SCN neurons for several days in culture. The chloride ratio (R) demonstrated circadian rhythmicity in AVP + neurons and VIP + neurons, but was not detected in GFAP + astrocytes. R peaked between ZT 7 and ZT 8 in both AVP + and VIP + neurons. R rhythmicity was not dependent on the activity of several transmembrane chloride carriers, action potential generation, or the L-type voltage-gated calcium channels, but was sensitive to GABA antagonists. We conclude that [Cl] is under circadian regulation in both AVP + and VIP + neurons.
在成熟的视交叉上核(SCN)中存在抑制性和兴奋性 GABA 传递,SCN 是生理节律的主起搏器。GABA 是抑制性还是兴奋性取决于细胞内氯离子浓度 ([Cl])。在这里,我们使用遗传编码的比率探针 Cl-Sensor,在培养的几天内研究了 AVP 和 VIP 表达 SCN 神经元中的 [Cl]。氯离子比(R)在 AVP+神经元和 VIP+神经元中表现出昼夜节律性,但在 GFAP+星形胶质细胞中未检测到。在 AVP+和 VIP+神经元中,R 在 ZT7 和 ZT8 之间达到峰值。R 的节律性不依赖于几种跨膜氯离子载体的活性、动作电位产生或 L 型电压门控钙通道,但对 GABA 拮抗剂敏感。我们得出结论,[Cl] 在 AVP+和 VIP+神经元中受到昼夜调节。