Skip to main content

Optogenetic Sensors for Monitoring Intracellular Chloride

  • Chapter
Optogenetics

Abstract

Here we provide an overview of genetically encoded chloride indicators and their application in imaging intracellular chloride concentration ([Cl]i). We first compare different chloride sensors and then describe the basic properties of two of these - Clomeleon and SuperClomeleon - in terms of their anion selectivity, pH sensitivity, and binding kinetics. We also describe several approaches that can be used to express Clomeleon in selected populations of neurons. Clomeleon imaging has been used to determine resting [Cl]i in a variety of neuron types and to determine the shifts in resting [Cl]i that occur during neuronal development and during pathological conditions. Clomeleon imaging has also been used to monitor dynamic changes in [Cl]i that are associated with activity of inhibitory synapses. Thus, optogenetic chloride imaging has provided a wide range of novel information about [Cl]i in neurons and should be generally useful for measuring [Cl]i within cells.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  • Adams SR, Harootunian AT, Buechler YJ et al (1991) Fluorescence ratio imaging of cyclic AMP in single cells. Nature 349(6311):694–697

    CAS  PubMed  Google Scholar 

  • Aickin CC, Brading AF (1982) Measurement of intracellular chloride in guinea-pig vas deferens by ion analysis, 36chloride efflux and micro-electrodes. J Physiol Lond 326:139–154

    CAS  PubMed Central  PubMed  Google Scholar 

  • Akerman CJ, Cline HT (2006) Depolarizing GABAergic conductances regulate the balance of excitation to inhibition in the developing retinotectal circuit in vivo. J Neurosci 26(19):5117–5130

    CAS  PubMed  Google Scholar 

  • Allen NJ, Attwell D (2004) The effect of simulated ischaemia on spontaneous GABA release in area CA1 of the juvenile rat hippocampus. J Physiol Lond 561(Pt 2):485–498

    CAS  PubMed Central  PubMed  Google Scholar 

  • Allen NJ, Rossi DJ, Attwell D (2004) Sequential release of GABA by exocytosis and reversed uptake leads to neuronal swelling in simulated ischemia of hippocampal slices. J Neurosci 24(15):3837–3849

    CAS  PubMed  Google Scholar 

  • Arosio D, Ricci F, Marchetti L et al (2010) Simultaneous intracellular chloride and pH measurements using a GFP-based sensor. Nat Methods 7(7):516–518

    CAS  PubMed  Google Scholar 

  • Barmashenko G, Hefft S, Aertsen A et al (2011) Positive shifts of the GABAA receptor reversal potential due to altered chloride homeostasis is widespread after status epilepticus. Epilepsia 52(9):1570–1578

    CAS  PubMed  Google Scholar 

  • Ben-Ari Y, Cherubini E, Corradetti R et al (1989) Giant synaptic potentials in immature rat CA3 hippocampal neurones. J Physiol Lond 416:303–325

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berglund K, Dunbar RL, Lee P et al (2005) A practical guide: imaging synaptic inhibition with Clomeleon, a genetically encoded chloride indicator. In: Konnerth A, Yuste R (eds) Imaging in neuroscience and development: a laboratory manual. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 595–598

    Google Scholar 

  • Berglund K, Schleich W, Krieger P et al (2006) Imaging synaptic inhibition in transgenic mice expressing the chloride indicator, Clomeleon. Brain Cell Biol 35(4–6):207–228

    CAS  PubMed Central  PubMed  Google Scholar 

  • Berglund K, Schleich W, Wang H et al (2008) Imaging synaptic inhibition throughout the brain via genetically targeted Clomeleon. Brain Cell Biol 36(1–4):101–118

    PubMed Central  PubMed  Google Scholar 

  • Berglund K, Kuner T, Augustine GJ (2009) Clomeleon, a genetically encoded chloride indicator. In: Alvarez-Leefmans FJ, Delpire E (eds) Physiology and pathology of chloride transporters and channels in the nervous system. Academic Press, London, pp 125–139

    Google Scholar 

  • Berglund K, Kuner T, Feng G et al (2011) Imaging synaptic inhibition with the genetically encoded chloride indicator Clomeleon. Cold Spring Harb Protoc 2011(12):1492–1497

    PubMed  Google Scholar 

  • Bertollini C, Murana E, Mosca L et al (2012) Transient increase in neuronal chloride concentration by neuroactive amino acids released from glioma cells. Front Mol Neurosci 5. doi:10.3389/fnmol.2012.00100

    Google Scholar 

  • Billups D, Attwell D (2002) Control of intracellular chloride concentration and GABA response polarity in rat retinal ON bipolar cells. J Physiol Lond 545(Pt 1):183–198

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bortone D, Polleux F (2009) KCC2 expression promotes the termination of cortical interneuron migration in a voltage-sensitive calcium-dependent manner. Neuron 62(1):53–71

    CAS  PubMed Central  PubMed  Google Scholar 

  • Bregestovski P, Waseem T, Mukhtarov M (2009) Genetically encoded optical sensors for monitoring of intracellular chloride and chloride-selective channel activity. Front Mol Neurosci 2. doi:10.3389/neuro.02.015.2009

    Google Scholar 

  • Bright GR, Fisher GW, Rogowska J et al (1989) Fluorescence ratio imaging microscopy. Methods Cell Biol 30:157–192

    CAS  PubMed  Google Scholar 

  • Brochiero E, Banderali U, Lindenthal S et al (1995) Basolateral membrane chloride permeability of A6 cells: implication in cell volume regulation. Pflugers Arch 431(1):32–45

    CAS  PubMed  Google Scholar 

  • Brown AM, Sutton RB, Walker JL Jr (1970) Increased chloride conductance as the proximate cause of hydrogen ion concentration effects in Aplysia neurons. J Gen Physiol 56(5):559–582

    CAS  PubMed Central  PubMed  Google Scholar 

  • Buzsáki G, Chrobak JJ (1995) Temporal structure in spatially organized neuronal ensembles: a role for interneuronal networks. Curr Opin Neurobiol 5(4):504–510

    PubMed  Google Scholar 

  • Caroni P (1997) Overexpression of growth-associated proteins in the neurons of adult transgenic mice. J Neurosci Methods 71(1):3–9

    CAS  PubMed  Google Scholar 

  • Chao AC, Dix JA, Sellers MC et al (1989) Fluorescence measurement of chloride transport in monolayer cultured cells. Mechanisms of chloride transport in fibroblasts. Biophys J 56(6):1071–1081

    CAS  PubMed Central  PubMed  Google Scholar 

  • Chao AC, Widdicombe JH, Verkman AS (1990) Chloride conductive and cotransport mechanisms in cultures of canine tracheal epithelial cells measured by an entrapped fluorescent indicator. J Membr Biol 113(3):193–202

    CAS  PubMed  Google Scholar 

  • Chen PY, Illsley NP, Verkman AS (1988) Renal brush-border chloride transport mechanisms characterized using a fluorescent indicator. Am J Physiol 254(1 Pt 2):F114–F120

    CAS  PubMed  Google Scholar 

  • Cheng L, Fu J, Tsukamoto A et al (1996) Use of green fluorescent protein variants to monitor gene transfer and expression in mammalian cells. Nat Biotechnol 14(5):606–609

    CAS  PubMed  Google Scholar 

  • Cherubini E, Gaiarsa JL, Ben-Ari Y (1991) GABA: an excitatory transmitter in early postnatal life. Trends Neurosci 14(12):515–519

    CAS  PubMed  Google Scholar 

  • Chesler M, Kaila K (1992) Modulation of pH by neuronal activity. Trends Neurosci 15(10):396–402

    CAS  PubMed  Google Scholar 

  • Chu TC, Socci RR, Coca-Prados M et al (1992) Comparative studies of furosemide effects on membrane potential and intracellular chloride activity in human and rabbit ciliary epithelium. Ophthalmic Res 24(2):83–91

    CAS  PubMed  Google Scholar 

  • Coskun T, Baumgartner HK, Chu S et al (2002) Coordinated regulation of gastric chloride secretion with both acid and alkali secretion. Am J Physiol Gastrointest Liver Physiol 283(5):G1147–G1155

    CAS  PubMed  Google Scholar 

  • Coull JA, Boudreau D, Bachand K et al (2003) Trans-synaptic shift in anion gradient in spinal lamina I neurons as a mechanism of neuropathic pain. Nature 424(6951):938–942

    CAS  PubMed  Google Scholar 

  • Coull JA, Beggs S, Boudreau D et al (2005) BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature 438(7070):1017–1021

    CAS  PubMed  Google Scholar 

  • De Koninck Y (2007) Altered chloride homeostasis in neurological disorders: a new target. Curr Opin Pharmacol 7(1):93–99

    PubMed  Google Scholar 

  • Deisz RA, Lehmann TN, Horn P et al (2011) Components of neuronal chloride transport in rat and human neocortex. J Physiol Lond 589(Pt 6):1317–1347

    CAS  PubMed Central  PubMed  Google Scholar 

  • Delpire E, Days E, Lewis LM et al (2009) Small-molecule screen identifies inhibitors of the neuronal K-Cl cotransporter KCC2. Proc Natl Acad Sci U S A 106(13):5383–5388

    CAS  PubMed Central  PubMed  Google Scholar 

  • Derdikman D, Hildesheim R, Ahissar E et al (2003) Imaging spatiotemporal dynamics of surround inhibition in the barrels somatosensory cortex. J Neurosci 23(8):3100–3105

    CAS  PubMed  Google Scholar 

  • Dickson RM, Cubitt AB, Tsien RY et al (1997) On/off blinking and switching behaviour of single molecules of green fluorescent protein. Nature 388(6640):355–358

    CAS  PubMed  Google Scholar 

  • Duebel J, Haverkamp S, Schleich W et al (2006) Two-photon imaging reveals somatodendritic chloride gradient in retinal ON-type bipolar cells expressing the biosensor Clomeleon. Neuron 49(1):81–94

    CAS  PubMed  Google Scholar 

  • Dzhala VI, Kuchibhotla KV, Glykys JC et al (2010) Progressive NKCC1-dependent neuronal chloride accumulation during neonatal seizures. J Neurosci 30(35):11745–11761

    CAS  PubMed Central  PubMed  Google Scholar 

  • Dzhala V, Valeeva G, Glykys J et al (2012) Traumatic alterations in GABA signaling disrupt hippocampal network activity in the developing brain. J Neurosci 32(12):4017–4031

    CAS  PubMed Central  PubMed  Google Scholar 

  • Elsliger M-A, Wachter RM, Hanson GT et al (1999) Structural and spectral response of green fluorescent protein variants to changes in pH. Biochemistry 38(17):5296–5301

    CAS  PubMed  Google Scholar 

  • Engblom AC, Åkerman KE (1993) Determination of the intracellular free chloride concentration in rat brain synaptoneurosomes using a chloride-sensitive fluorescent indicator. Biochim Biophys Acta 1153(2):262–266

    CAS  PubMed  Google Scholar 

  • Engblom AC, Holopainen I, Åkerman KE (1989) Determination of GABA receptor-linked Cl fluxes in rat cerebellar granule cells using a fluorescent probe SPQ. Neurosci Lett 104(3):326–330

    CAS  PubMed  Google Scholar 

  • Engblom AC, Holopainen I, Åkerman KE (1991) Ethanol-induced Cl flux in rat cerebellar granule cells as measured by a fluorescent probe. Brain Res 568(1–2):55–60

    CAS  PubMed  Google Scholar 

  • Feng G, Mellor RH, Bernstein M et al (2000) Imaging neuronal subsets in transgenic mice expressing multiple spectral variants of GFP. Neuron 28(1):41–51

    CAS  PubMed  Google Scholar 

  • Foskett JK (1990) [Ca2+]i modulation of Cl content controls cell volume in single salivary acinar cells during fluid secretion. Am J Physiol 259(6 Pt 1):C998–C1004

    CAS  PubMed  Google Scholar 

  • Freund TF, Buzsáki G (1996) Interneurons of the hippocampus. Hippocampus 6(4):347–470

    CAS  PubMed  Google Scholar 

  • Friedel P, Bregestovski P, Medina I (2013) Improved method for efficient imaging of intracellular Cl with Cl-sensor using conventional fluorescence setup. Front Mol Neurosci 6. doi:10.3389/fnmol.2013.00007

    Google Scholar 

  • Funk K, Woitecki A, Franjic-Würtz C et al (2008) Modulation of chloride homeostasis by inflammatory mediators in dorsal root ganglion neurons. Mol Pain 4:32

    PubMed Central  PubMed  Google Scholar 

  • Gagnon M, Bergeron MJ, Lavertu G et al (2013) Chloride extrusion enhancers as novel therapeutics for neurological diseases. Nat Med 19(11):1524–1528

    CAS  PubMed Central  PubMed  Google Scholar 

  • Galietta LJ, Haggie PM, Verkman AS (2001) Green fluorescent protein-based halide indicators with improved chloride and iodide affinities. FEBS Lett 499(3):220–224

    CAS  PubMed  Google Scholar 

  • Glykys J, Dzhala V, Egawa K et al (2014) Local impermeant anions establish the neuronal chloride concentration. Science 343(6171):670–675

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grimley JS, Li L, Wang W et al (2013) Visualization of synaptic inhibition with an optogenetic sensor developed by cell-free protein engineering automation. J Neurosci 33(41):16297–16309

    CAS  PubMed Central  PubMed  Google Scholar 

  • Grynkiewicz G, Poenie M, Tsien RY (1985) A new generation of Ca2+ indicators with greatly improved fluorescence properties. J Biol Chem 260(6):3440–3450

    CAS  PubMed  Google Scholar 

  • Hasan MT, Friedrich RW, Euler T et al (2004) Functional fluorescent Ca2+ indicator proteins in transgenic mice under TET control. PLoS Biol 2(6):e163. doi:10.1371/journal.pbio.0020163

    PubMed Central  PubMed  Google Scholar 

  • Haverkamp S, Wassle H, Duebel J et al (2005) The primordial, blue-cone color system of the mouse retina. J Neurosci 25(22):5438–5445

    CAS  PubMed  Google Scholar 

  • Heim R (1999) Green fluorescent protein forms for energy transfer. Methods Enzymol 302:408–423

    CAS  PubMed  Google Scholar 

  • Helmchen F, Denk W (2005) Deep tissue two-photon microscopy. Nat Methods 2(12):932–940

    CAS  PubMed  Google Scholar 

  • Heo KS, Ryoo SW, Kim L et al (2008) Cl-channel is essential for LDL-induced cell proliferation via the activation of Erk1/2 and PI3k/Akt and the upregulation of Egr-1 in human aortic smooth muscle cells. Mol Cells 26(5):468–473

    CAS  PubMed  Google Scholar 

  • Hinkle M, Heller P, Van der Kloot W (1971) The influence of potassium and chloride ions on the membrane potential of single muscle fibers of the crayfish. Comp Biochem Physiol A 40(1):181–201

    CAS  PubMed  Google Scholar 

  • Illsley NP, Verkman AS (1987) Membrane chloride transport measured using a chloride-sensitive fluorescent probe. Biochemistry 26(5):1215–1219

    CAS  PubMed  Google Scholar 

  • Inglefield JR, Schwartz-Bloom RD (1997) Confocal imaging of intracellular chloride in living brain slices: measurement of GABAA receptor activity. J Neurosci Methods 75(2):127–135

    CAS  PubMed  Google Scholar 

  • Inglefield JR, Schwartz-Bloom RD (1999) Using confocal microscopy and the fluorescent indicator, 6-methoxy-N-ethylquinolinium iodide, to measure changes in intracellular chloride. Methods Enzymol 307:469–481

    CAS  PubMed  Google Scholar 

  • Jayaraman S, Haggie P, Wachter RM et al (2000) Mechanism and cellular applications of a green fluorescent protein-based halide sensor. J Biol Chem 275(9):6047–6050

    CAS  PubMed  Google Scholar 

  • Jose M, Nair DK, Reissner C et al (2007) Photophysics of Clomeleon by FLIM: discriminating excited state reactions along neuronal development. Biophys J 92(6):2237–2254

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaila K, Pasternack M, Saarikoski J et al (1989) Influence of GABA-gated bicarbonate conductance on potential, current and intracellular chloride in crayfish muscle fibres. J Physiol Lond 416:161–181

    CAS  PubMed Central  PubMed  Google Scholar 

  • Kaneko H, Nakamura T, Lindemann B (2001) Noninvasive measurement of chloride concentration in rat olfactory receptor cells with use of a fluorescent dye. Am J Physiol Cell Physiol 280(6):C1387–C1393

    CAS  PubMed  Google Scholar 

  • Kerem B, Rommens JM, Buchanan JA et al (1989) Identification of the cystic fibrosis gene: genetic analysis. Science 245(4922):1073–1080

    CAS  PubMed  Google Scholar 

  • Khirug S, Yamada J, Afzalov R et al (2008) GABAergic depolarization of the axon initial segment in cortical principal neurons is caused by the Na-K-2Cl cotransporter NKCC1. J Neurosci 28(18):4635–4639

    CAS  PubMed  Google Scholar 

  • Kneen M, Farinas J, Li Y et al (1998) Green fluorescent protein as a noninvasive intracellular pH indicator. Biophys J 74(3):1591–1599

    CAS  PubMed Central  PubMed  Google Scholar 

  • Koncz C, Daugirdas JT (1994) Use of MQAE for measurement of intracellular [Cl] in cultured aortic smooth muscle cells. Am J Physiol 267(6 Pt 2):H2114–H2123

    CAS  PubMed  Google Scholar 

  • Kovalchuk Y, Garaschuk O (2012) Two-photon chloride imaging using MQAE in vitro and in vivo. Cold Spring Harb Protoc 2012(7):778–785

    PubMed  Google Scholar 

  • Krapf R, Berry CA, Verkman AS (1988a) Estimation of intracellular chloride activity in isolated perfused rabbit proximal convoluted tubules using a fluorescent indicator. Biophys J 53(6):955–962

    CAS  PubMed Central  PubMed  Google Scholar 

  • Krapf R, Illsley NP, Tseng HC et al (1988b) Structure-activity relationships of chloride-sensitive fluorescent indicators for biological application. Anal Biochem 169(1):142–150

    CAS  PubMed  Google Scholar 

  • Krieger P, Kuner T, Sakmann B (2007) Synaptic connections between layer 5B pyramidal neurons in mouse somatosensory cortex are independent of apical dendrite bundling. J Neurosci 27(43):11473–11482

    CAS  PubMed  Google Scholar 

  • Kuner T, Augustine GJ (2000) A genetically encoded ratiometric indicator for chloride: capturing chloride transients in cultured hippocampal neurons. Neuron 27(3):447–459

    CAS  PubMed  Google Scholar 

  • Liedtke W, Yeo M, Zhang H et al (2013) Highly conductive carbon nanotube matrix accelerates developmental chloride extrusion in central nervous system neurons by increased expression of chloride transporter KCC2. Small 9(7):1066–1075

    CAS  PubMed  Google Scholar 

  • Lillis KP, Kramer MA, Mertz J et al (2012) Pyramidal cells accumulate chloride at seizure onset. Neurobiol Dis 47(3):358–366

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lindsly C, Gonzalez-Islas C, Wenner P (2014) Activity blockade and GABAA receptor blockade produce synaptic scaling through chloride accumulation in embryonic spinal motoneurons and interneurons. PLoS One 9(4):e94559. doi:10.1371/journal.pone.0094559

    PubMed Central  PubMed  Google Scholar 

  • Llopis J, McCaffery JM, Miyawaki A et al (1998) Measurement of cytosolic, mitochondrial, and Golgi pH in single living cells with green fluorescent proteins. Proc Natl Acad Sci U S A 95(12):6803–6808

    CAS  PubMed Central  PubMed  Google Scholar 

  • Lorenzen I, Aberle T, Plieth C (2004) Salt stress-induced chloride flux: a study using transgenic Arabidopsis expressing a fluorescent anion probe. Plant J 38(3):539–544

    CAS  PubMed  Google Scholar 

  • Maglova LM, Crowe WE, Smith PR et al (1998) Na+-K+-Cl cotransport in human fibroblasts is inhibited by cytomegalovirus infection. Am J Physiol 275(5 Pt 1):C1330–C1341

    CAS  PubMed  Google Scholar 

  • Marandi N, Konnerth A, Garaschuk O (2002) Two-photon chloride imaging in neurons of brain slices. Pfluegers Arch/Eur J Physiol 445(3):357–365

    CAS  Google Scholar 

  • Markova O, Mukhtarov M, Real E et al (2008) Genetically encoded chloride indicator with improved sensitivity. J Neurosci Methods 170(1):67–76

    CAS  PubMed  Google Scholar 

  • Metzger F, Repunte-Canonigo V, Matsushita S et al (2002) Transgenic mice expressing a pH and Cl sensing yellow-fluorescent protein under the control of a potassium channel promoter. Eur J Neurosci 15(1):40–50

    PubMed  Google Scholar 

  • Miesenböck G, De Angelis DA, Rothman JE (1998) Visualizing secretion and synaptic transmission with pH-sensitive green fluorescent proteins. Nature 394(6689):192–195

    PubMed  Google Scholar 

  • Miller RF, Dacheux RF (1983) Intracellular chloride in retinal neurons: measurement and meaning. Vision Res 23(4):399–411

    CAS  PubMed  Google Scholar 

  • Miyawaki A, Llopis J, Heim R et al (1997) Fluorescent indicators for Ca2+ based on green fluorescent proteins and calmodulin. Nature 388(6645):882–887

    CAS  PubMed  Google Scholar 

  • Miyawaki A, Griesbeck O, Heim R et al (1999) Dynamic and quantitative Ca2+ measurements using improved cameleons. Proc Natl Acad Sci U S A 96(5):2135–2140

    CAS  PubMed Central  PubMed  Google Scholar 

  • Miyawaki A, Nagai T, Mizuno H (2005) Engineering fluorescent proteins. Adv Biochem Eng Biotechnol 95:1–15

    CAS  PubMed  Google Scholar 

  • Mukhtarov M, Liguori L, Waseem T et al (2013) Calibration and functional analysis of three genetically encoded Cl/pH sensors. Front Mol Neurosci 6. doi:10.3389/fnmol.2013.00009

    Google Scholar 

  • Nakamura T, Kaneko H, Nishida N (1997) Direct measurement of the chloride concentration in newt olfactory receptors with the fluorescent probe. Neurosci Lett 237(1):5–8

    CAS  PubMed  Google Scholar 

  • Ormö M, Cubitt AB, Kallio K et al (1996) Crystal structure of the Aequorea victoria green fluorescent protein. Science 273(5280):1392–1395

    PubMed  Google Scholar 

  • Owens DF, Boyce LH, Davis MB et al (1996) Excitatory GABA responses in embryonic and neonatal cortical slices demonstrated by gramicidin perforated-patch recordings and calcium imaging. J Neurosci 16(20):6414–6423

    CAS  PubMed  Google Scholar 

  • Palma E, Amici M, Sobrero F et al (2006) Anomalous levels of Cl transporters in the hippocampal subiculum from temporal lobe epilepsy patients make GABA excitatory. Proc Natl Acad Sci 103(22):8465–8468

    CAS  PubMed Central  PubMed  Google Scholar 

  • Paulsen O, Moser EI (1998) A model of hippocampal memory encoding and retrieval: GABAergic control of synaptic plasticity. Trends Neurosci 21(7):273–278

    CAS  PubMed  Google Scholar 

  • Payne JA, Rivera C, Voipio J et al (2003) Cation-chloride co-transporters in neuronal communication, development and trauma. Trends Neurosci 26(4):199–206

    CAS  PubMed  Google Scholar 

  • Pologruto TA, Yasuda R, Svoboda K (2004) Monitoring neural activity and [Ca2+] with genetically encoded Ca2+ indicators. J Neurosci 24(43):9572–9579

    CAS  PubMed  Google Scholar 

  • Pond BB, Berglund K, Kuner T et al (2006) The chloride transporter Na+-K+-Cl cotransporter isoform-1 contributes to intracellular chloride increases after in vitro ischemia. J Neurosci 26(5):1396–1406

    CAS  PubMed  Google Scholar 

  • Raimondo JV, Joyce B, Kay L et al (2013) A genetically-encoded chloride and pH sensor for dissociating ion dynamics in the nervous system. Front Cell Neurosci 7. doi:10.3389/fncel.2013.00202

    Google Scholar 

  • Reiff DF, Ihring A, Guerrero G et al (2005) In vivo performance of genetically encoded indicators of neural activity in flies. J Neurosci 25(19):4766–4778

    CAS  PubMed Central  PubMed  Google Scholar 

  • Rink TJ, Tsien RY, Pozzan T (1982) Cytoplasmic pH and free Mg2+ in lymphocytes. J Cell Biol 95(1):189–196

    CAS  PubMed  Google Scholar 

  • Rivera C, Voipio J, Payne JA et al (1999) The K+/Cl co-transporter KCC2 renders GABA hyperpolarizing during neuronal maturation. Nature 397(6716):251–255

    CAS  PubMed  Google Scholar 

  • Russell JM, Boron WF (1976) Role of chloride transport in regulation of intracellular pH. Nature 264(5581):73–74

    CAS  PubMed  Google Scholar 

  • Saito K, Chang YF, Horikawa K et al (2012) Luminescent proteins for high-speed single-cell and whole-body imaging. Nat Commun 3:1262. doi:10.1038/ncomms2248

    PubMed Central  PubMed  Google Scholar 

  • Sakai R, Repunte-Canonigo V, Raj CD et al (2001) Design and characterization of a DNA-encoded, voltage-sensitive fluorescent protein. Eur J Neurosci 13(12):2314–2318

    CAS  PubMed  Google Scholar 

  • Satoh H, Kaneda M, Kaneko A (2001) Intracellular chloride concentration is higher in rod bipolar cells than in cone bipolar cells of the mouse retina. Neurosci Lett 310(2–3):161–164

    CAS  PubMed  Google Scholar 

  • Servetnyk Z, Roomans GM (2007) Chloride transport in NCL-SG3 sweat gland cells: channels involved. Exp Mol Pathol 83(1):47–53

    CAS  PubMed  Google Scholar 

  • Sinnecker D, Voigt P, Hellwig N et al (2005) Reversible photobleaching of enhanced green fluorescent proteins. Biochem Wash 44(18):7085–7094

    CAS  Google Scholar 

  • Slemmer JE, Matsushita S, De Zeeuw CI et al (2004) Glutamate-induced elevations in intracellular chloride concentration in hippocampal cell cultures derived from EYFP-expressing mice. Eur J Neurosci 19(11):2915–2922

    PubMed  Google Scholar 

  • Somogyi P, Klausberger T (2005) Defined types of cortical interneurone structure space and spike timing in the hippocampus. J Physiol Lond 562(Pt 1):9–26

    CAS  PubMed Central  PubMed  Google Scholar 

  • Song L, Seeger A, Santos-Sacchi J (2005) On membrane motor activity and chloride flux in the outer hair cell: lessons learned from the environmental toxin tributyltin. Biophys J 88(3):2350–2362

    CAS  PubMed Central  PubMed  Google Scholar 

  • Staley KJ, Proctor WR (1999) Modulation of mammalian dendritic GABAA receptor function by the kinetics of Cl and HCO3 transport. J Physiol Lond 519(Pt 3):693–712

    CAS  PubMed Central  PubMed  Google Scholar 

  • Stein V, Hermans-Borgmeyer I, Jentsch TJ et al (2004) Expression of the KCl cotransporter KCC2 parallels neuronal maturation and the emergence of low intracellular chloride. J Comp Neurol 468(1):57–64

    CAS  PubMed  Google Scholar 

  • Suzuki M, Morita T, Iwamoto T (2006) Diversity of Cl channels. Cell Mol Life Sci 63(1):12–24

    CAS  PubMed Central  PubMed  Google Scholar 

  • Szabadics J, Varga C, Molnár G et al (2006) Excitatory effect of GABAergic axo-axonic cells in cortical microcircuits. Science 311(5758):233–235

    CAS  PubMed  Google Scholar 

  • Torsney C, MacDermott AB (2005) Neuroscience: a painful factor. Nature 438(7070):923–925

    CAS  PubMed  Google Scholar 

  • Tsien RY (1980) New calcium indicators and buffers with high selectivity against magnesium and protons: design, synthesis, and properties of prototype structures. Biochemistry 19(11):2396–2404

    CAS  PubMed  Google Scholar 

  • Verkman AS, Sellers MC, Chao AC et al (1989) Synthesis and characterization of improved chloride-sensitive fluorescent indicators for biological applications. Anal Biochem 178(2):355–361

    CAS  PubMed  Google Scholar 

  • Wachter RM, Remington SJ (1999) Sensitivity of the yellow variant of green fluorescent protein to halides and nitrate. Curr Biol 9(17):R628–R629

    CAS  PubMed  Google Scholar 

  • Wachter RM, Elsliger MA, Kallio K et al (1998) Structural basis of spectral shifts in the yellow-emission variants of green fluorescent protein. Structure 6(10):1267–1277

    CAS  PubMed  Google Scholar 

  • Wachter RM, Yarbrough D, Kallio K et al (2000) Crystallographic and energetic analysis of binding of selected anions to the yellow variants of green fluorescent protein. J Mol Biol 301(1):157–171

    CAS  PubMed  Google Scholar 

  • Walker JL, Brown HM (1977) Intracellular ionic activity measurements in nerve and muscle. Physiol Rev 57(4):729–778

    CAS  PubMed  Google Scholar 

  • Waseem T, Mukhtarov M, Buldakova S et al (2010) Genetically encoded Cl-Sensor as a tool for monitoring of Cl-dependent processes in small neuronal compartments. J Neurosci Methods 193(1):14–23

    CAS  PubMed  Google Scholar 

  • White HS, Brown SD, Woodhead JH et al (1997) Topiramate enhances GABA-mediated chloride flux and GABA-evoked chloride currents in murine brain neurons and increases seizure threshold. Epilepsy Res 28(3):167–179

    CAS  PubMed  Google Scholar 

  • Wolfbeis O, Urbano E (1983) Eine fluorimetrische, schwermetallfreie Methode zur Analyse von Chlor, Brom und Iod in organischen Materialien. Z Anal Chem 314(6):577–581

    CAS  Google Scholar 

  • Yeo M, Berglund K, Augustine G et al (2009) Novel repression of Kcc2 transcription by REST-RE-1 controls developmental switch in neuronal chloride. J Neurosci 29(46):14652–14662

    CAS  PubMed Central  PubMed  Google Scholar 

  • Yeo M, Berglund K, Hanna M et al (2013) Bisphenol A delays the perinatal chloride shift in cortical neurons by epigenetic effects on the Kcc2 promoter. Proc Natl Acad Sci U S A 110(11):4315–4320

    CAS  PubMed Central  PubMed  Google Scholar 

  • Zhang G, Gurtu V, Kain SR (1996) An enhanced green fluorescent protein allows sensitive detection of gene transfer in mammalian cells. Biochem Biophys Res Commun 227(3):707–711

    CAS  PubMed  Google Scholar 

Download references

Acknowledgments

Writing of this chapter was supported by a CRP grant from the National Research Foundation of Singapore and by the World Class Institute (WCI) Program of the National Research Foundation of Korea (NRF) funded by the Ministry of Education, Science and Technology of Korea (MEST) (NRF Grant Number: WCI 2009–003).

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to George J. Augustine .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer Japan

About this chapter

Cite this chapter

Berglund, K., Wen, L., Augustine, G.J. (2015). Optogenetic Sensors for Monitoring Intracellular Chloride. In: Yawo, H., Kandori, H., Koizumi, A. (eds) Optogenetics. Springer, Tokyo. https://doi.org/10.1007/978-4-431-55516-2_11

Download citation

Publish with us

Policies and ethics