title: Regulation of synaptic transmission at the photoreceptor terminal: a novel role for the cation-chloride co-transporter NKCC1.
abstract: 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.
authors.affiliation: Department of Biomedical Science, Charles E Schmidt College of Medicine, Florida Atlantic University, 777 Glades Road, Boca Raton, FL 33431, USA. wshen@fau.edu
authors.forename: Wen
authors.initials: W
authors.lastname: Shen
authors.forename: Lauren A
authors.initials: LA
authors.lastname: Purpura
authors.forename: Baoqin
authors.initials: B
authors.lastname: Li
authors.forename: Changlong
authors.initials: C
authors.lastname: Nan
authors.forename: Irene J
authors.initials: IJ
authors.lastname: Chang
authors.forename: Harris
authors.initials: H
authors.lastname: Ripps
mesh_terms: D000557:Ambystoma; D000818:Animals; D002034:Bumetanide / Q000494:pharmacology; D002118:Calcium / Q000502:physiology; D004298:Dopamine / Q000502:physiology; D010786:Photoreceptor Cells / Q000502:physiology*; D028021:Sodium-Potassium-Chloride Symporters / Q000502:physiology*; D064506:Solute Carrier Family 12, Member 2; D009435:Synaptic Transmission / Q000502:physiology*
chemical_list: D028021:Sodium-Potassium-Chloride Symporters; D064506:Solute Carrier Family 12, Member 2; D002034:Bumetanide; D002118:Calcium; D004298:Dopamine