Classification of chloride channelscAMP-activated chloride channel(Cysticfibrosistransmembraneconductanceregulator,CFTR)activatedbycyclicAMP-dependentphosphorylationCalcium activated chloride channels (CaCCs)Voltagegatedchloridechannels(CiCs)Ligand-gated chloridechannels(GABA(y-aminobutyricacid)andglycineactivated)Swelling-activated chloride channels(Volume regulatedchloridechannels)Putative intracellularchloride channels
Classification of chloride channels cAMP-activated chloride channel (Cystic fibrosis transmembrane conductance regulator, CFTR) activated by cyclic AMP-dependent phosphorylation Calcium activated chloride channels (CaCCs) Voltage gated chloride channels (ClCs) Ligand-gated chloride channels (GABA ( -aminobutyric acid) and glycine activated) Swelling-activated chloride channels (Volume regulated chloride channels) Putative intracellular chloride channels
StructuralclassesofClchannelsExtracellularligand-gatedCI-channels(ELG)Cysticfibrosistransmembraneconductanceregulator(CFTR)Voltage-gatedchloridechannels(CLC)Nucleotidesensitivechloridechannel(CLNS1A):VolumesensitiveChlorideintracellularchannelsCalciumactivated:Mediate a calcium-activatedchlorideconductance
Structural classes of Cl- channels Extracellular ligand-gated Cl- channels (ELG) Cystic fibrosis transmembrane conductance regulator (CFTR) Voltage-gated chloride channels (CLC) Nucleotide sensitive chloride channel (CLNS1A): Volume sensitive Chloride intracellular channels Calcium activated: Mediate a calcium-activated chloride conductance
Extracellular ligand-gated Clchannels(ELG)4transmembranedomainsineachsubunitReceptorsfunctionaspentamersTypes·PostsynapticGABA&glycinereceptors
Extracellular ligand-gated Cl- channels (ELG) 4 transmembrane domains in each subunit Receptors function as pentamers Types Post synaptic GABA & glycine receptors
Voltage-gated chloridechannels(CiC)Membrane-associatedpartofCiC channelsis composed of17α-helicesHelixAis not inserted into the membraneMostofthehelicesarenotperpendiculartothemembrane,butseverelytiltedHelicesmaynotspanthewidthofthebilayerCarboxyterminusofeukaryoticCiCproteinshastwoCBSdomainsUnspecified role in protein-protein interactionCiCchannelsaredimers:Eachmonomerhasonepore(double-barreledchannels)CIC-KproteinsAssociatewiththeβ-subunitbarttinwhichspansthemembranetwice
Voltage-gated chloride channels (ClC) Membrane-associated part of ClC channels is composed of 17 -helices Helix A is not inserted into the membrane Most of the helices are not perpendicular to the membrane, but severely tilted Helices may not span the width of the bilayer Carboxy terminus of eukaryotic ClC proteins has two CBS domains Unspecified role in protein-protein interaction ClC channels are dimers: Each monomer has one pore (double-barreled channels) ClC-K proteins Associate with the -subunit barttin which spans the membrane twice
CIC channeltypesCLCN-1Skeletalmuscle,PlacentaVoltagestabilizationMutation disorders:Myotonia;ParamyotoniaCLCN-2·UbiquitousCellvolumeregulationActivatedbyhyperpolarization,cell swelling&acidicpHMutationdisorders:ldiopathic generalizedepilepsiesCLCN-3Brain,Kidney(TypeB intercalatedcells),Skeletalmuscle,Lung,RetinaIntracellularEndosomes&Synapticvesicles·Knockout:Degenerationof hippocampus &retina
ClC channel types CLCN-1 Skeletal muscle, Placenta Voltage stabilization Mutation disorders: Myotonia; Paramyotonia CLCN-2 Ubiquitous Cell volume regulation Activated by hyperpolarization, cell swelling & acidic pH Mutation disorders: Idiopathic generalized epilepsies CLCN-3 Brain, Kidney (Type B intercalated cells), Skeletal muscle, Lung, Retina Intracellular Endosomes & Synaptic vesicles Knockout: Degeneration of hippocampus & retina