Mitochondrial potassiumm transport:the role ofthe MitoKATP WeiGuo2005.1.14
Mitochondrial potassium transport: the role of the MitoKATP WeiGuo 2005.1.14
Mitochondrial potassium cycle Mitochondria are structurally complex.The inner membrane contains the essential the electron transport proteins and exchange carriers
Mitochondrial potassium cycle • Mitochondria are structurally complex. The inner membrane contains the essential components of the electron transport proteins and all of the exchange carriers
Mitochondrial potassium cycle The mitochondrial K+cycle consists of influx and eux pathways forK,H and anion These ions are exchanged between the matrixand the intermembrane space (IMS however,the outer membrane (OM)does not present a barrier to further exchange of small ions with the cytosol
Mitochondrial potassium cycle • The mitochondrial K+ cycle consists of influx and efflux pathways for K+ , H+ , and anions • These ions are exchanged between the matrix and the intermembrane space ( IMS ); however, the outer membrane (OM) does not present a barrier to further exchange of small ions with the cytosol
Influx pathway for potassium matrix K+ K Pi- Matrix MitoKATP K"leak ETS alkalinization △Ψ SUR Pi-H+ IMS symporter OH- ,Electron transport system(ETS)generates membrane potential(△Ψ， .AY can drive K+influx by diffusion("K+leak")and via the mitoKATP. This K+for H+exchange will alkalinize the matrix,causing phosphate to enter via the Pi-H*symporter
Influx pathway for potassium IMS matrix MitoKATP K + leak K+ K+ H+ ETS ∆Ψ Matrix alkalinization PiOHPi-H+ symporter ⚫ Electron transport system (ETS) generates membrane potential (∆Ψ). ⚫ ∆Ψ can drive K+ influx by diffusion (‘‘K+ leak’’) and via the mitoKATP. ⚫ This K+ for H+ exchange will alkalinize the matrix, causing phosphate to enter via the Pi-H+ symporter
Efflux pathway for potassium Net uptake of K+salts will be accompanied by osmotically obligated water,esunx swelling.Excess matrix K+is then ejected by th K+/H+antiporter H MitoKATP K"/H' K-H* antiporter UR K
Efflux pathway for potassium • Net uptake of K+ salts will be accompanied by osmotically obligated water, resulting in matrix swelling. Excess matrix K+ is then ejected by the K+ /H+ antiporter K +-H+ antiporter
Early work on the potassium cycle Diffusive K+influx would be sufficient to cause matrix water content to increase.withntal lysis.This would be avoided by the K+ antiporter
Early work on the potassium cycle • Diffusive K+ influx would be sufficient to cause matrix water content to increase, with eventual lysis. This would be avoided by the K+ /H+ antiporter
MitoKATp meets a different need in volume regulation Maintain matrix volume mito-KATP synthesizing ATP at very high rates △Ψdecreases matrix contraction
synthesizing ATP at very high rates ∆Ψ decreases matrix contraction mito-KATP Maintain matrix volume MitoKATP meets a different need in volume regulation
MitoKArp on matrix and IMS volumes MitoKArp opening was shown to regulate matrix volume during ischemia and state 3 respiration matrix volume return to DE original state 10-15%contraction in matrix volume 5-HD Addition of antimycin A to simulate ischemia depolarization and decrease in diffusive addition of ADP to trigger K*influx state 3 respiration
MitoKATP on matrix and IMS volumes • MitoKATP opening was shown to regulate matrix volume during ischemia and state 3 respiration Addition of antimycin A to simulate ischemia DE depolarization and decrease in diffusive K+ addition of ADP to trigger influx state 3 respiration 10–15% contraction in matrix volume matrix volume return to original state 5-HD
MitoKATp on matrix and IMS volumes Changes in IMS could be estimated by means of membrane surface areas(SA) .Studies shown that mitok opening decfeae IMS volume Physiological changes in matrix volume may have important effects on IMS structure function
MitoKATP on matrix and IMS volumes • Changes in IMS could be estimated by means of membrane surface areas (SA) • Studies shown that mitoKATP opening decreases IMS volume • Physiological changes in matrix volume may have important effects on IMS structure–function
Two distinct consequences of opening mitoK ·When△is high→opening mitoKAT mar alkalinizationproduction of reactive ogen species (ROS) ·When△平is depressed→opening mitoKr prevent contraction of the matrix and expansion of the IMS
Two distinct consequences of opening mitoKATP • When ∆Ψ is high → opening mitoKATP → matrix alkalinization → production of reactive oxygen species (ROS) ↑ • When ∆Ψ is depressed → opening mitoKATP → prevent contraction of the matrix and expansion of the IMS