{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T10:14:34Z","timestamp":1790763274299,"version":"4.1.0"},"reference-count":54,"publisher":"Wiley","issue":"1","license":[{"start":{"date-parts":[[2012,11,21]],"date-time":"2012-11-21T00:00:00Z","timestamp":1353456000000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["The Journal of Physiology"],"published-print":{"date-parts":[[2013,1]]},"abstract":"<jats:title>Key points<\/jats:title><jats:p><jats:list list-type=\"explicit-label\">\n<jats:list-item><jats:p>The Cl<jats:sup>\u2212<\/jats:sup> uptake cotransporter, Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u20132Cl<jats:sup>\u2212<\/jats:sup> type 1 (NKCC1), is expressed in the distal synaptic layer of the vertebrate retina, where photoreceptor terminals contact the dendrites of horizontal and bipolar cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Light adaptation, dopamine and a D1 receptor agonist increased the expression levels of phosphorylated NKCC1, the active form of the transporter inserted in the cell membrane.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Pharmacological blockage of NKCC1 with bumetanide increased the rod\u2010 and cone\u2010mediated excitatory postsynaptic currents in horizontal cells.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>Inhibiting NKCC1 increased exocytotic membrane capacitance, intracellular Ca<jats:sup>2+<\/jats:sup> levels, and voltage\u2010dependent Ca<jats:sup>2+<\/jats:sup> channel currents in both rod and cone terminals, all of which are associated with increased transmitter release.<\/jats:p><\/jats:list-item>\n<jats:list-item><jats:p>This study describes a new function of NKCC1, specifically the suppression of transmitter release at the photoreceptor terminals, a process that serves to prevent the depletion of glutamate and protect retinal neurons from its putative cytotoxic effects.<\/jats:p><\/jats:list-item>\n<\/jats:list><\/jats:p><jats:p><jats:bold>Abstract\u2002<\/jats:bold> The Na<jats:sup>+<\/jats:sup>\u2013K<jats:sup>+<\/jats:sup>\u20132Cl<jats:sup>\u2212<\/jats:sup> co\u2010transporter 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\u2013horizontal 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\u2010transports 1 Na<jats:sup>+<\/jats:sup>, 1 K<jats:sup>+<\/jats:sup> and 2 Cl<jats:sup>\u2212<\/jats:sup>, 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<jats:sup>2+<\/jats:sup>\u2010dependent 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\u2010induced release of dopamine acting on D1\u2010like receptors. In sum, our study reveals a new role for NKCC1 in the regulation of synaptic transmission in photoreceptors.<\/jats:p>","DOI":"10.1113\/jphysiol.2012.241042","type":"journal-article","created":{"date-parts":[[2012,10,23]],"date-time":"2012-10-23T04:56:22Z","timestamp":1350968182000},"page":"133-147","source":"Crossref","is-referenced-by-count":10,"title":["Regulation of synaptic transmission at the photoreceptor terminal: a novel role for the cation\u2013chloride co\u2010transporter NKCC1"],"prefix":"10.1113","volume":"591","author":[{"given":"Wen","family":"Shen","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lauren A.","family":"Purpura","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Baoqin","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Changlong","family":"Nan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Irene J.","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Harris","family":"Ripps","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2012,11,21]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.2008.06194.x"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.056168"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.1991.sp018887"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.exer.2008.06.013"},{"key":"e_1_2_6_6_1","doi-asserted-by":"publisher","DOI":"10.1007\/s12035-010-8147-z"},{"key":"e_1_2_6_7_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.5750-07.2008"},{"key":"e_1_2_6_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0002839"},{"key":"e_1_2_6_9_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2003.056168"},{"key":"e_1_2_6_10_1","first-page":"309","article-title":"Cation\u2010chloride cotransporters in neuronal communication","volume":"15","author":"Delpire E","year":"2000","journal-title":"News Physiol Sci"},{"key":"e_1_2_6_11_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.190769"},{"key":"e_1_2_6_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/9713"},{"key":"e_1_2_6_13_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523807070629"},{"key":"e_1_2_6_14_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00284.2004"},{"key":"e_1_2_6_15_1","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M206294200"},{"key":"e_1_2_6_16_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.00011.2004"},{"key":"e_1_2_6_17_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0604551103"},{"key":"e_1_2_6_18_1","doi-asserted-by":"publisher","DOI":"10.1016\/0005-2736(80)90446-0"},{"key":"e_1_2_6_19_1","doi-asserted-by":"publisher","DOI":"10.1023\/A:1020521308985"},{"key":"e_1_2_6_20_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.194738"},{"key":"e_1_2_6_21_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523800008348"},{"key":"e_1_2_6_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/nn.2267"},{"key":"e_1_2_6_23_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncpneuro0883"},{"key":"e_1_2_6_24_1","first-page":"2377","article-title":"Physiology and biophysics of chloride and cation cotransport across cell membranes","volume":"46","author":"Lauf PK","year":"1987","journal-title":"Fed Proc"},{"key":"e_1_2_6_25_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuropharm.2009.06.041"},{"key":"e_1_2_6_26_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523808080164"},{"key":"e_1_2_6_27_1","doi-asserted-by":"publisher","DOI":"10.1097\/WNR.0b013e3280ba49b0"},{"key":"e_1_2_6_28_1","doi-asserted-by":"publisher","DOI":"10.1006\/meth.2001.1262"},{"key":"e_1_2_6_29_1","doi-asserted-by":"crossref","first-page":"435S","DOI":"10.1093\/ajh\/4.7.435S","article-title":"Diltiazem inhibition of sodium\u2010induced calcium release. Effects on energy metabolism of heart mitochondria","volume":"7","author":"Matlib MA","year":"1991","journal-title":"Am J Hypertens"},{"key":"e_1_2_6_30_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(83)90087-1"},{"key":"e_1_2_6_31_1","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1096-9861(19990906)411:4<705::AID-CNE14>3.0.CO;2-Y"},{"key":"e_1_2_6_32_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523800012207"},{"key":"e_1_2_6_33_1","doi-asserted-by":"publisher","DOI":"10.1097\/00006982-198202040-00020"},{"key":"e_1_2_6_34_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2008.151050"},{"key":"e_1_2_6_35_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.1377-08.2009"},{"key":"e_1_2_6_36_1","doi-asserted-by":"publisher","DOI":"10.1523\/JNEUROSCI.4298-04.2005"},{"key":"e_1_2_6_37_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.neuron.2005.02.002"},{"key":"e_1_2_6_38_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2002.023671"},{"key":"e_1_2_6_39_1","doi-asserted-by":"publisher","DOI":"10.1113\/jphysiol.2010.191437"},{"key":"e_1_2_6_40_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0038985"},{"key":"e_1_2_6_41_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.01099.2004"},{"key":"e_1_2_6_42_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-006-9118-2"},{"key":"e_1_2_6_43_1","doi-asserted-by":"publisher","DOI":"10.1007\/s11373-008-9263-x"},{"key":"e_1_2_6_44_1","doi-asserted-by":"publisher","DOI":"10.1016\/0028-3908(95)00128-S"},{"key":"e_1_2_6_45_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523806232127"},{"key":"e_1_2_6_46_1","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2202-5-53"},{"key":"e_1_2_6_47_1","doi-asserted-by":"publisher","DOI":"10.1152\/jn.00932.2002"},{"key":"e_1_2_6_48_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523800172025"},{"key":"e_1_2_6_49_1","doi-asserted-by":"publisher","DOI":"10.1017\/S0952523802192017"},{"key":"e_1_2_6_50_1","doi-asserted-by":"publisher","DOI":"10.1111\/j.1460-9568.1996.tb01192.x"},{"key":"e_1_2_6_51_1","doi-asserted-by":"publisher","DOI":"10.1023\/B:DOOP.0000019487.88486.0a"},{"key":"e_1_2_6_52_1","doi-asserted-by":"publisher","DOI":"10.1016\/0014-4835(88)90009-7"},{"key":"e_1_2_6_53_1","doi-asserted-by":"publisher","DOI":"10.1016\/0042-6989(93)90219-M"},{"key":"e_1_2_6_54_1","doi-asserted-by":"publisher","DOI":"10.1016\/S0006-8993(98)00373-4"},{"key":"e_1_2_6_55_1","doi-asserted-by":"publisher","DOI":"10.1002\/cne.21100"}],"container-title":["The Journal of Physiology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/api.wiley.com\/onlinelibrary\/tdm\/v1\/articles\/10.1113%2Fjphysiol.2012.241042","content-type":"unspecified","content-version":"vor","intended-application":"text-mining"},{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/pdf\/10.1113\/jphysiol.2012.241042","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,10,28]],"date-time":"2023-10-28T19:24:58Z","timestamp":1698521098000},"score":1,"resource":{"primary":{"URL":"https:\/\/physoc.onlinelibrary.wiley.com\/doi\/10.1113\/jphysiol.2012.241042"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2012,11,21]]},"references-count":54,"journal-issue":{"issue":"1","published-print":{"date-parts":[[2013,1]]}},"alternative-id":["10.1113\/jphysiol.2012.241042"],"URL":"https:\/\/doi.org\/10.1113\/jphysiol.2012.241042","archive":["Portico"],"relation":{},"ISSN":["0022-3751","1469-7793"],"issn-type":[{"value":"0022-3751","type":"print"},{"value":"1469-7793","type":"electronic"}],"subject":[],"published":{"date-parts":[[2012,11,21]]}}}