Two Types of Cl Transporters Contribute to the Regulation of Intracellular Cl Concentrations in ON- and OFF-type Bipolar Cells in the Mouse Retina. (1st August 2020)

• Record Type: Journal Article
• Authors: Yin, Chengzhu; Ishii, Toshiyuki; Kaneda, Makoto
• Is Part Of: Neuroscience. Volume 440(2020)
• Page Start: 267
• Page End: 276
• Publication Date: 2020-08-01
• Subjects: HEPES 4-(2-Hydroxyethyl)piperazine-1-ethanesulfonic acid -- KCC2 K-Cl co-transporter -- NCBE sodium-driven chloride bicarbonate exchanger -- NK3R neurokinin 3 receptor -- NKCC1 Na-K-Cl co-transporter -- PBS phosphate-buffered saline -- PKC protein kinase C alpha; mouse retina -- bipolar cell -- NKCC1 -- KCC2; Neurochemistry -- Periodicals; Neurophysiology -- Periodicals; Neurology -- Periodicals; Neurochimie -- Périodiques; Neurophysiologie -- Périodiques; Neurochemistry; Neurophysiology; Electronic journals; Periodicals; Electronic journals; 612.8
• DOI: 10.1016/j.neuroscience.2020.06.004
• Languages: English
• ISSNs: 0306-4522

Abstract

Highlights: Intracellular Cl − concentrations ([Cl − ]i ) were higher in rod (ON-type) bipolar cells (BCs) than in OFF-type BCs. [Cl − ]i was regulated by two types of Cl transporters (NKCC1 and KCC2) in rod (ON-type) and OFF-type BCs. [Cl − ]i was mainly regulated by NKCC1 in rod (ON-type) BCs and by KCC2 in OFF-type BCs. Differences in [Cl − ]i are important for the formation of two types of surround responses in retinal BCs. Abstract: In the retina, ON- and OFF-type bipolar cells are classified by subtype-specific center responses, which are attributed to differences in glutamate receptor subtypes. However, the mechanisms by which ON- and OFF-type bipolar cells generate subtype-specific surround responses remain unclear. One hypothesis for surround responses is that intracellular Cl concentrations ([Cl-]i ) are set at different levels to achieve opposite polarities for GABA responses in ON- and OFF-type bipolar cells. Although this hypothesis is supported by previous findings obtained from rod (ON-) type bipolar cells, there is currently no information on OFF-type bipolar cells. In the present study, we examined the distribution and function of the Cl transporters, the Na-K-Cl co-transporter (NKCC1) and K-Cl co-transporter (KCC2), in rod (ON-) and OFF-type bipolar cells using immunohistochemical, in situ hybridization, and electrophysiological methods. Rod (ON-) and OFF-type bipolar cells both expressed NKCC1 and KCC2. However, the functional contribution of NKCC1 and KCC2 to the regulation of [Cl − ]i differed between rod (ON-) and OFF-type bipolar cells. Strong NKCC1 activity increased [Cl − ]i in rod (ON-) type bipolar cells, while that of KCC2 decreased [Cl − ]i in OFF-type bipolar cells. We also confirmed the presence of a [Cl − ]i gradient between dendrites and axon terminals in rod (ON-type) bipolar cells. Thus, the subtype-specific control of [Cl − ]i is achieved by the activity of NKCC1 relative to that of KCC2 and appears to influence the polarity of surround responses.