Structureof K+channelsPotassium channelshave a tetrameric structure inwhich fouridentical proteinsubunits associateto forma four-foldsymmetric(C4)complexarrangedaround acentralionconducting pore (i.e.,a homotetramer).Alternatively four relatedbutnotidentical proteinsubunitsmay associateto formheterotetramericcomplexes withpseudo C4 symmetry.All potassium channel subunits have a distinctive pore-loopstructurethat linesthe top oftheporeand isresponsibleforpotassiumselectivepermeability.Thereare over 8o mammaliangenesthat encode potassiumchannelsubunitsUsing X-ray crystallography,profound insights have beengainedinto howpotassium ions passthroughthese channelsand why(smaller)sodiumionsdonot
Structure of K+ channels Potassium channels have a tetrameric structure in which four identical protein subunits associate to form a four-fold symmetric (C4) complex arranged around a central ion conducting pore (i.e., a homotetramer). Alternatively four related but not identical protein subunits may associate to form heterotetrameric complexes with pseudo C4 symmetry. All potassium channel subunits have a distinctive pore-loop structure that lines the top of the pore and is responsible for potassium selective permeability. There are over 80 mammalian genes that encode potassium channel subunits. Using X-ray crystallography, profound insights have been gained into how potassium ions pass through these channels and why (smaller) sodium ions do not
Dr.JohnRoderickRockefellerwonthe2oo3NobelPrize in Chemistry fordiscoveriesconcerningchannelsincellmembranesa Howard Hughes Medical Institute (HHMl) investigator at TheRockefellerUniversity,amemberoftheNationalAcademyofSciencesdetermined thethree-dimensional structure of a pore thatallows cellsto controltheirintake of potassiumionssolved a riddlethat has perplexed biophysicists for decades:Howdoesapotassiumchanneladmit millionsofpotassiumionspersecond,whileallowingonlyonesmallersodiumiontoslipthroughforevery1,ooopotassiumions?
Dr. John Roderick Rockefeller won the 2003 Nobel Prize in Chemistry for discoveries concerning channels in cell membranes a Howard Hughes Medical Institute (HHMI) investigator at The Rockefeller University, a member of the National Academy of Sciences determined the three-dimensional structure of a pore that allows cells to control their intake of potassium ions solved a riddle that has perplexed biophysicists for decades: How does a potassium channel admit millions of potassium ions per second, while allowing only one smaller sodium ion to slip through for every 1,000 potassium ions?
PassageofKtionsthroughthechannelsElectronDensityAlongthelonPathwayK+ions are partially dehydrated before enteringthe selectivity filterGreenball:KionContouredat1sigmaK+ions arefully dehydrated in the selectivity filter000Green ball: K* ionRed ball:WaterContoured at2 sigmaK+ ions are fully rehydrated in the cavityGreenball:K*ionRedball:WaterTwosubunitsoftheKcsAtetramerareshownasanq-carbontraceinyellowcolor.Contouredat2sigmaElectrondensity iscontouredat2sigma
Passage of K+ ions through the channels
ClassesofKtchannelsCalcium-activatedpotassiumchannelopeninresponseto the presenceof calcium ionsorothersignallingmolecules.Inwardly rectifyingpotassium channelpasses current (positive charge)more easily in the inwarddirection (intothe cell)Tandemporedomainpotassiumchannelareconstitutivelyopenorpossesshighbasalactivationsuchasthe"restingpotassium channels"or"leakchannels"that setthe negativemembrane potential ofneurons.Whenopen,theyallowpotassiumionstocrossthe membraneat arate whichis nearlyasfast as theirdiffusionthrough bulk water.Voltage-gated potassium channelare voltage-gated ion channels that open or closeinresponseto changes inthetransmembranevoltage
Classes of K+ channels Calcium-activated potassium channel open in response to the presence of calcium ions or other signalling molecules. Inwardly rectifying potassium channel passes current (positive charge) more easily in the inward direction (into the cell). Tandem pore domain potassium channel are constitutively open or possess high basal activation, such as the "resting potassium channels" or "leak channels" that set the negative membrane potential of neurons. When open, they allow potassium ions to cross the membrane at a rate which is nearly as fast as their diffusion through bulk water. Voltage-gated potassium channel are voltage-gated ion channels that open or close in response to changes in the transmembrane voltage
Potassiumchannelclasses,functionand pharmacologyClassSubclassesFunctionBlockersActivators.1-EBIO.BK channelCalcium-activated.apamin inhibition following stimuli increasing intracellular calciumNS3096I&1P?SK channel.charybdotoxinCyPPAROMK(K-1.1)·Nonselective:Ba?+Csrecyclingandsecretion ofpotassiuminnephrons none.GPCRregulated·GPCR antagonistsInwardly rectifying?mediate the inhibitory effect of manyGPCRsGPCRagonists(K,3.x)·ifenprodil5]2I&1Pglibenclamidediazoxide-ATP-sensitive (K.6.x)closewhenATP is hightopromoteinsulin secretion:tolbutamide:pinacidil:TWIKTandem pore:TRAAK.Contributetorestingpotential:halothanedomain:none.TREK4I&2P-TASK?tetraethylammoniumactionpotentialrepolanization.hERG(Kv11.1):retigabine(K.7)Voltage-gated:4-aminopyndine:limitsfrequencyofactionpotentials(disturbances cause1B16I&1P:KMQT1(K,7.1):dendrotoxins(somedysrhythmia)types)
Potassium channel classes, function, and pharmacology