@article{52e56452814b453d9fdea58f44e89950,
title = "Cloning and functional expression of the cDNA encoding an inwardly-rectifying potassium channel expressed in pancreatic β-cells and in the brain",
abstract = "A cDNA clone encoding an inwardly-rectifying K-channel (BIR1) was isolated from insulinoma cells. The predicted amino acid sequence shares 72% identity with the cardiac ATP-sensitive K-channel rcKATP (KATP-1; [6]). The mRNA is expressed in the brain and insulinoma cells. Heterologous expression in Xenopus oocytes produced currents which were K+-selective, time-independent and showed inward rectification. The currents were blocked by external barium and caesium, but insensitive to tolbutamide and diazoxide. In inside-out patches, channel activity was not blocked by 1 mM internal ATP. The sequence homology with KATP-1 suggests that BIR1 is a subunit of a brain and β-cell KATP channel. However, pharmacological differences and the lack of ATP-sensitivity, suggest that if, this is the case, heterologous subunits must exert strong modulatory influences on the native channel.",
keywords = "ATP-sensitive K-channel, BIR1, Inward rectifyer, K-channel, Pancreatic β-cell",
author = "Bond, {C. T.} and C. {\"A}mm{\"a}l{\"a} and R. Ashfield and Blair, {T. A.} and F. Gribble and Khan, {R. N.} and K. Lee and P. Proks and Rowe, {I. C.M.} and H. Sakura and Ashford, {M. J.} and Adelman, {J. P.} and Ashcroft, {F. M.}",
note = "Funding Information: The resultsp resentehde red emonstratteh atBIR1 encodes an inwardly-rectifyiKng-c hanneel xpresseidn both pancreatic fl-cellsa nd in brain. Two pieceso f evidences uggestth atBIR1 may represenat pore-formingsu bunitof the fl-cell KATp channel.F irst, the predicteadm inoa cids equencseh ares7 2%i dentityw ithKATp-1. Secondlyw, hene xpresseidn oocytest,h ew hole-celBl IR1 cur-rentsa reK +-selectivtei,m e-independeanntd b lockedb y external applicationo f caesiuma nd barium,p ropertiews hich are sharedw ith nativeK ATP channels\[ 6,18,19\]. In most respectsh, owever,t he heterologousleyx pressed BIR1 channeld iffers from the nativef l-cell KAT P channel. Firstly, BIR 1 currentsa re insensitivteo intracellulaArT P, to sulfonylureaasn dto potassiumch anneol penersS. econdlyt,h e whole-cell currents showed strong inward rectification, whereatsh atof the nativefl -cellKAT P channeils weak.T hirdly, the Ba2 +b lockof whole-cecllu rrentiss far lessv oltage-dependent than thato f the nativec hanne(lu npublisheodb servations). Fourthlyt,h ek ineticsc, onductancaen dr ectificatiopnr operties of the mostc ommonm odeo f behaviou(rm ode1 ) at the single channelle vela revery differenftr om thoseo f the nativefl -cell KAT P channelF. urthermorea,l thoughth e singlec hannecl on-ductancein mode2 at -60 mV resembletsh atof native/~-cell KAT p channelt,h e kineticsa nd rectificatiopnr opertieasr e not similar. Heterologousleyx presseBd IRI channelsn ormallyg atein mode 1 in which eventsa ppearfl ickerya nd unresolvedT.h is behaviouirs reminiscenotf the rapid block of the conduction pathwayo f voltage-gateKd-channelsb y externaTl EA. For BIR1 channelsm, ode1 activityp ersistes veni n excisedp atches and with solutionsw hich do not containp otentiabl locking cationss ucha s Mg 2+a ndp olyaminesO.n ee xplanatiofno r the two differentm odeso f gatingi s that in mode 1 part of the intracelluladro maino f thec hanneml ayact to blockt hep erme-ationp athwayI.n wardc urrentsfl owingt hrought hepore may transientlyre lievet he block by briefly forcing the blocking particleo ut of the permeatiopna thwayI.f this blockinga nd unblockingo ccurvery fast, open eventsw ill not be fully re-solveda nds inglec hannecl urrentsw ill appeaar s rapidf lickers of reducedc onductanceO.u twardc urrentsm ay enhanceth e block by forcing the blockingp articlef urtheri nto the pore. Mode 2 behavioumr ayr esultif theb lockingp articleis removed completelfyr om the vicinityo f the pore, unmaskingth e fully openedp ropertieosf the channelI.f this is the case,t henthe nativec hanneml ayn ormallys howm ode2 behaviouirf additional subunitsw hichform part of the channecl omplexa lter the conformatioonf the blockingp articles o that it is no longer free to entert hep ermeatiopna thway. In conclusionw, e havei dentifieda n inwardr ectifieKr -channel subunitw hichis expresseidn brain and,B-cellsB. IR1 has significanht omologyto KATp-1.H owever,i f BIR1 represents a pore-lbrminsgu bunito f thef l-cellKAT p channetl henassoci-ateds ubunitsh avep rofounde ffectso n the channepl roperties, includingm odulatioonf gatinga nd of sensitivittyo ATE AcknowledgemenWtse: t hankD rs.Jim Maylie,A rmandoL agruttaan d Paul Smithf or fruitfuld iscussioann de nthusiasmTh. is workw ass up-portedb y grantsf rom NIH (J.P.A.), Glaxo (J.P.A.), the Wellcome Trust( F.M.A., M.L.J.A.), the BritishD iabeticA ssociatio(nF .M.A.), and the MedicalR esearchC ouncil of the UK (F.M.A.). H.S. was supportebdy a JSPS Fellowship.",
year = "1995",
month = jun,
day = "19",
doi = "10.1016/0014-5793(95)00497-W",
language = "English (US)",
volume = "367",
pages = "61--66",
journal = "FEBS Letters",
issn = "0014-5793",
publisher = "Elsevier",
number = "1",
}