ChloridechannelsConsiderablylessattentionhasbeengiventochloridechannels.This is partly because their identificationandanalysishaslaggedbehindthoseofothertargets,andbecauseoftechnicalchallengesinscreeningforchloridechannelmodulatorsElectrophysiologists havehistoricallyconsideredanionchannel currents asunimportantleaks'associated withcationchannelsinexcitablecells.Chloridechannelsdisplayavarietyof importantphysiological and cellular roles that include regulation of pHvolumehomeostasis,organicsolutetransport,cell migrationcellproliferationand differentiation
Chloride channels Considerably less attention has been given to chloride channels. This is partly because their identification and analysis has lagged behind those of other targets, and because of technical challenges in screening for chloride channel modulators. Electrophysiologists have historically considered anion channel currents as ‘unimportant leaks’ associated with cation channels in excitable cells. Chloride channels display a variety of important physiological and cellular roles that include regulation of pH, volume homeostasis, organic solute transport, cell migration, cell proliferation and differentiation
ChloridechannelsA largemoleculardiversityof Cl-channels.Chloridechannelsare a superfamily of poorly understood ion channelsconsistingofapproximately13membersClchannelsmaybeclassifiedastotheirlocalization(plasmamembranevs.vesicular),single-channelconductance,ormechanism ofregulation.However,suchclassificationschemes are ambiguous.The most logical classification of Clchannelswill be basedontheirmolecularstructuresBasedonsequencehomologytheClchannelscanbesubdivided intoanumber ofgroupsTheimportanceofonesuchgroup,theCLCfamilyof Clchannels,canbeseenfromthediseasesthatdevelopwhenthechanneldoes notfunctionnormally
Chloride channels A large molecular diversity of Cl- channels. Chloride channels are a superfamily of poorly understood ion channels consisting of approximately 13 members. Cl- channels may be classified as to their localization (plasma membrane vs. vesicular), single-channel conductance, or mechanism of regulation. However, such classification schemes are ambiguous. The most logical classification of Clchannels will be based on their molecular structures. Based on sequence homology the Cl- channels can be subdivided into a number of groups. The importance of one such group, the CLC family of Clchannels, can be seen from the diseases that develop when the channel does not function normally
FunctionsofCl-channelsClchannelsmay performtheirfunctionsintheplasmamembrane or in membranes of intracellularorganelles.On theonehand,thesefunctions arerelatedtothetransportofcharge, i.e.,to the electric current flowing through the channel.and on the other hand to the transport of matter.AllowthepassivediffusionofnegativelychargedionsalongelectrochemicalgradientPlasmamembraneCl-currentsareimportantfortheregulationof excitability in nerve and muscle.Currents flowing throughintracellular Cl-channels arethought to ensure the overallelectroneutraltransportoftheelectrogenicH-ATPasethatacidifiesseveralintracellularcompartments
Functions of Cl- channels Cl- channels may perform their functions in the plasma membrane or in membranes of intracellular organelles. On the one hand, these functions are related to the transport of charge, i.e., to the electric current flowing through the channel, and on the other hand to the transport of matter. Allow the passive diffusion of negatively charged ions along electrochemical gradient Plasma membrane Cl- currents are important for the regulation of excitability in nerve and muscle. Currents flowing through intracellular Cl- channels are thought to ensure the overall electroneutral transport of the electrogenic H-ATPase that acidifies several intracellular compartments
FunctionsofCl-channelsChloride channels are important for setting cell restingmembrane.Bulk flow of chloride is important for cell volume regulation,as well as fortransepithelial transport.These channelsconduct Claswell as otheranionssuchasHcO3,I,SCN,andNO3.May conduct otheranions(e.g.,I-orNO3)betterthanCl.Functionsoftenrelatedtotransport of chargeThe regulation of Cl-channel activity by anions implies thatchanges in intracellular Cl-concentration ([Cl]) may have aregulatoryrole.Cl-doesnotseemtoplaya roleas intracellularmessenger
Functions of Cl- channels Chloride channels are important for setting cell resting membrane. Bulk flow of chloride is important for cell volume regulation, as well as for transepithelial transport. These channels conduct Cl- as well as other anions such as HCO 3 -, I-, SCN-, and NO 3 -. May conduct other anions (e.g., I- or NO 3 -) better than Cl-. Functions often related to transport of charge. The regulation of Cl- channel activity by anions implies that changes in intracellular Cl- concentration ([Cl- ]i ) may have a regulatory role. Cl- does not seem to play a role as intracellular messenger
ClassificationschemesLocalization:Plasmamembranevs.vesicularSingle-channelconductanceMechanismofregulationMolecularstructure
Classification schemes Localization: Plasma membrane vs. vesicular Single-channel conductance Mechanism of regulation Molecular structure