CIC channel typesCLCN-4Muscle, Brain,Heart, Kidney,RetinaVesicularchannelCLCN-5Kidney (TypeA intercalated cells)Endosomalchannel·Renalendocytosis?CreabsorptionCLCN-6UbiquitousIntracellularCLCN6-nullmiceReducedpainsensitivityBehavioralabnormalitiesEnlargedproximalaxonswithautofluorescentelectron-densematerial,containinglysosomalproteins
ClC channel types CLCN-4 Muscle, Brain, Heart, Kidney, Retina Vesicular channel CLCN-5 Kidney (Type A intercalated cells) Endosomal channel Renal endocytosis ? Cl- reabsorption CLCN-6 Ubiquitous Intracellular CLCN6-null mice Reduced pain sensitivity Behavioral abnormalities Enlarged proximal axons with autofluorescent electron-dense material, containing lysosomal proteins
ClCchanneltypesCLCN-7Brain;Testes;Skeletal muscle;KidneyLysosomalMutations:OsteopetrosisCiC-O:Torpedo electric organ Cl-channelCiC-K/barttinchannels:Transepithelial transportin kidney&innerearCLC-K1(CICN-KA):KidneyTransepithelialCl-transportLocation:Thinascending limb of Henleloopin renal innermedullaPlaysroleinurineconcentrationCLC-K2 (CICN-KB)Kidney?ClreabsorptionBarttersyndrometypes3&4
ClC channel types CLCN-7 Brain; Testes; Skeletal muscle; Kidney Lysosomal Mutations: Osteopetrosis ClC-0: Torpedo electric organ Cl- channel ClC-K/barttin channels: Transepithelial transport in kidney & inner ear CLC-K1 (ClCN-KA): Kidney Transepithelial Cl- transport Location: Thin ascending limb of Henle loop in renal inner medulla Plays role in urine concentration CLC-K2 (ClCN-KB) Kidney ? Cl- reabsorption Bartter syndrome types 3 & 4
ClCproteinstructureBlue:cystathionine-β-synthase(CBS)domainsGreen:membranesegmentsYellow:boundClRed:theintracellularproton-bindingsiteE2o3
ClC protein structure Blue: cystathionine- -synthase (CBS) domains Green: membrane segments Yellow: bound Cl − Red: the intracellular proton-binding site E203
Chlorideintracellular channelsGeneralLocation:NuclearorplasmamembraneNomembranespanningdomainsFoundvacuolarorganellesFunction:Electrolytecomposition&acidificationofintravesicularspacesCLIC1:NuclearCLiC2:Skeletalmuscle;fetalliverCLIC3:Plasmamembrane;interactswithErk7CLiC4:Brain,heart,placenta,skeletal muscleRole:Developmentofvascularcollateralsinskeletalmuscle&brainCLIC5:Heart;skeletal muscle
Chloride intracellular channels General Location: Nuclear or plasma membrane No membrane spanning domains Found vacuolar organelles Function: Electrolyte composition & acidification of intravesicular spaces CLIC1: Nuclear CLIC2: Skeletal muscle; fetal liver CLIC3: Plasma membrane; interacts with Erk7 CLIC4: Brain, heart, placenta, skeletal muscle Role: Development of vascular collaterals in skeletal muscle & brain CLIC5: Heart; skeletal muscle
ChannelsofintracellularorganellesAnionchannels(ortransporters)areneededforthepassageofanionic substrateslikephosphate and sulfate out ofdegradative as well as biosynthetic compartments, e.g.,lysosomesandtheGolgiapparatus.Alarge-conductanceanionchannelofcardiacsarcoplasmatioreticulumisshownto conduct adenine nucleotides,butthephysiological roleof this conductanceremains elusiveAnion channelsareimplicated inorganellarvolumeregulation.Mitochondriaaresubjectto volume changes,dependingonthemetabolicstate ofthe cell.This isprobablymediated bythefluxof K+ and Cl-acrossthe inner mitochondrial membrane
Channels of intracellular organelles Anion channels (or transporters) are needed for the passage of anionic substrates like phosphate and sulfate out of degradative as well as biosynthetic compartments, e.g., lysosomes and the Golgi apparatus. A large-conductance anion channel of cardiac sarcoplasmatic reticulum is shown to conduct adenine nucleotides, but the physiological role of this conductance remains elusive. Anion channels are implicated in organellar volume regulation. Mitochondria are subject to volume changes, depending on the metabolic state of the cell. This is probably mediated by the flux of K+ and Cl- across the inner mitochondrial membrane