PMID- 23090945 OWN - NLM STAT- MEDLINE DCOM- 20130613 LR - 20211021 IS - 1469-7793 (Electronic) IS - 0022-3751 (Print) IS - 0022-3751 (Linking) VI - 591 IP - 1 DP - 2013 Jan 1 TI - Regulation of synaptic transmission at the photoreceptor terminal: a novel role for the cation-chloride co-transporter NKCC1. PG - 133-47 LID - 10.1113/jphysiol.2012.241042 [doi] AB - The Na(+)-K(+)-2Cl(-) co-transporter type 1 (NKCC1) is localized primarily throughout the outer plexiform layer (OPL) of the distal retina, a synaptic lamina that is comprised of the axon terminals of photoreceptors and the dendrites of horizontal and bipolar cells. Although known to play a key role in development, signal transmission and the gating of sensory signals in other regions of the retina and in the CNS, the contribution of NKCC1 to synaptic transmission within the OPL is largely unknown. In the present study, we investigated the function of NKCC1 at the photoreceptor-horizontal cell synapse by recording the electrical responses of photoreceptors and horizontal cells before and after blocking the activity of the transporter with bumetanide (BMN). Because NKCC1 co-transports 1 Na(+), 1 K(+) and 2 Cl(-), it is electroneutral and its activation had little effect on membrane conductance. However, recordings from postsynaptic horizontal cells revealed that inhibiting NKCC1 with BMN greatly increased glutamate release from both rod and cone terminals. In addition, we found that NKCC1 directly regulates Ca(2+)-dependent exocytosis at the photoreceptor synapse, raising the possibility that NKCC1 serves to suppress bulk release of glutamate vesicles from photoreceptor terminals in the dark and at light offset. Interestingly, NKCC1 gene and protein expressions were upregulated by light, which we attribute to the light-induced release of dopamine acting on D1-like receptors. In sum, our study reveals a new role for NKCC1 in the regulation of synaptic transmission in photoreceptors. FAU - Shen, Wen AU - Shen W AD - Department of Biomedical Science, Charles E Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA. wshen@fau.edu FAU - Purpura, Lauren A AU - Purpura LA FAU - Li, Baoqin AU - Li B FAU - Nan, Changlong AU - Nan C FAU - Chang, Irene J AU - Chang IJ FAU - Ripps, Harris AU - Ripps H LA - eng GR - R01 EY014161/EY/NEI NIH HHS/United States GR - EY 14161/EY/NEI NIH HHS/United States PT - Journal Article PT - Research Support, N.I.H., Extramural PT - Research Support, U.S. Gov't, Non-P.H.S. DEP - 20121022 PL - England TA - J Physiol JT - The Journal of physiology JID - 0266262 RN - 0 (Sodium-Potassium-Chloride Symporters) RN - 0 (Solute Carrier Family 12, Member 2) RN - 0Y2S3XUQ5H (Bumetanide) RN - SY7Q814VUP (Calcium) RN - VTD58H1Z2X (Dopamine) SB - IM MH - Ambystoma MH - Animals MH - Bumetanide/pharmacology MH - Calcium/physiology MH - Dopamine/physiology MH - Photoreceptor Cells/*physiology MH - Sodium-Potassium-Chloride Symporters/*physiology MH - Solute Carrier Family 12, Member 2 MH - Synaptic Transmission/*physiology PMC - PMC3630777 EDAT- 2012/10/24 06:00 MHDA- 2013/06/14 06:00 PMCR- 2014/01/01 CRDT- 2012/10/24 06:00 PHST- 2012/10/24 06:00 [entrez] PHST- 2012/10/24 06:00 [pubmed] PHST- 2013/06/14 06:00 [medline] PHST- 2014/01/01 00:00 [pmc-release] AID - jphysiol.2012.241042 [pii] AID - 10.1113/jphysiol.2012.241042 [doi] PST - ppublish SO - J Physiol. 2013 Jan 1;591(1):133-47. doi: 10.1113/jphysiol.2012.241042. Epub 2012 Oct 22.