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Kir2.3 isoform confers pH sensitivity to heteromeric Kir2.1/Kir2.3 channels in HEK293 cells.
Muñoz V
,
Vaidyanathan R
,
Tolkacheva EG
,
Dhamoon AS
,
Taffet SM
,
Anumonwo JM
.
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Data on pH regulation of the cardiac potassium current I(K1) suggest species-dependent differences in the molecular composition of the underlying Kir2 channel proteins. The purpose of this study was to test the hypothesis that the presence of the Kir2.3 isoform in heterotetrameric channels modifies channel sensitivity to pH. Voltage clamp was performed on HEK293 cells stably expressing guinea pig Kir2.1 and/or Kir2.3 isoforms and on sheep cardiac ventricular myocytes at varying extracellular pH (pH(o)) and in the presence of CO(2) to determine the sensitivity of macroscopic currents to pH. Single-channel activity was recorded from the HEK293 stables to determine the mechanisms of the changes in whole cell current. Biophysical characteristics of whole-cell and single-channel currents in Kir2.1/Kir2.3 double stables displayed properties attributable to isoform heteromerization. Whole-cell Kir2.1/Kir2.3 currents rectified in a manner reminiscent of Kir2.1 but were significantly inhibited by extracellular acidification in the physiologic range (pK(a) approximately 7.4). Whole-cell currents were more sensitive to a combined extracellular and intracellular acidification produced by CO(2). At pH(o) = 6.0, unitary conductances of heteromeric channels were reduced. Ovine cardiac ventricular cell I(K1) was pH(o) and CO(2) sensitive, consistent with the expression of Kir2.1 and Kir2.3 in this species. Kir2.1 and Kir2.3 isoforms form heteromeric channels in HEK293. The presence of Kir2.3 subunit(s) in heteromeric channels confers pH sensitivity to the channels. The single and double stable cells presented in this study are useful models for studying physiologic regulation of heteromeric Kir2 channels in mammalian cells.
Anumonwo,
Proton and zinc effects on HERG currents.
1999, Pubmed,
Xenbase
Anumonwo,
Proton and zinc effects on HERG currents.
1999,
Pubmed
,
Xenbase
Avila,
Intramembrane charge movement associated with endogenous K+ channel activity in HEK-293 cells.
2004,
Pubmed
Cohen,
Binding of the inward rectifier K+ channel Kir 2.3 to PSD-95 is regulated by protein kinase A phosphorylation.
1996,
Pubmed
Coulter,
Identification and molecular localization of a pH-sensing domain for the inward rectifier potassium channel HIR.
1995,
Pubmed
,
Xenbase
Delmar,
Slow recovery of excitability and the Wenckebach phenomenon in the single guinea pig ventricular myocyte.
1989,
Pubmed
Dhamoon,
Unique Kir2.x properties determine regional and species differences in the cardiac inward rectifier K+ current.
2004,
Pubmed
Jiang,
Gating of inward rectifier K(+) channels by proton-mediated interactions of intracellular protein domains.
2002,
Pubmed
Komukai,
Electrophysiological response of rat atrial myocytes to acidosis.
2002,
Pubmed
Liu,
Comparison of cloned Kir2 channels with native inward rectifier K+ channels from guinea-pig cardiomyocytes.
2001,
Pubmed
,
Xenbase
Lopatin,
Inward rectifiers in the heart: an update on I(K1).
2001,
Pubmed
Pegan,
Cytoplasmic domain structures of Kir2.1 and Kir3.1 show sites for modulating gating and rectification.
2005,
Pubmed
,
Xenbase
Plaster,
Mutations in Kir2.1 cause the developmental and episodic electrical phenotypes of Andersen's syndrome.
2001,
Pubmed
,
Xenbase
Post,
pHe, [Ca2+]e, and cell death during metabolic inhibition: role of phospholipase A2 and sarcolemmal phospholipids.
1998,
Pubmed
Preisig-Müller,
Heteromerization of Kir2.x potassium channels contributes to the phenotype of Andersen's syndrome.
2002,
Pubmed
,
Xenbase
Priori,
A novel form of short QT syndrome (SQT3) is caused by a mutation in the KCNJ2 gene.
2005,
Pubmed
Qu,
Gating of inward rectifier K+ channels by proton-mediated interactions of N- and C-terminal domains.
2000,
Pubmed
,
Xenbase
Rook,
Physiologic function of I(K1) requires a combination of Kir2 isoforms.
2007,
Pubmed
Samie,
Rectification of the background potassium current: a determinant of rotor dynamics in ventricular fibrillation.
2001,
Pubmed
Schram,
Barium block of Kir2 and human cardiac inward rectifier currents: evidence for subunit-heteromeric contribution to native currents.
2003,
Pubmed
,
Xenbase
Schram,
Kir2.4 and Kir2.1 K(+) channel subunits co-assemble: a potential new contributor to inward rectifier current heterogeneity.
2002,
Pubmed
,
Xenbase
Shieh,
K+ binding sites and interactions between permeating K+ ions at the external pore mouth of an inward rectifier K+ channel (Kir2.1).
1999,
Pubmed
,
Xenbase
Shimoni,
Role of an inwardly rectifying potassium current in rabbit ventricular action potential.
1992,
Pubmed
Stanfield,
Constitutively active and G-protein coupled inward rectifier K+ channels: Kir2.0 and Kir3.0.
2002,
Pubmed
Tanemoto,
In vivo formation of a proton-sensitive K+ channel by heteromeric subunit assembly of Kir5.1 with Kir4.1.
2000,
Pubmed
Wang,
Differential distribution of inward rectifier potassium channel transcripts in human atrium versus ventricle.
1998,
Pubmed
Xu,
Intracellular protons inhibit transient outward K+ current in ventricular myocytes from diabetic rats.
1996,
Pubmed
Yan,
Different intracellular polyamine concentrations underlie the difference in the inward rectifier K(+) currents in atria and ventricles of the guinea-pig heart.
2005,
Pubmed
Yang,
Biophysical and molecular mechanisms underlying the modulation of heteromeric Kir4.1-Kir5.1 channels by CO2 and pH.
2000,
Pubmed
,
Xenbase
Yu,
Endogenous voltage-gated potassium channels in human embryonic kidney (HEK293) cells.
1998,
Pubmed
Zaritsky,
The consequences of disrupting cardiac inwardly rectifying K(+) current (I(K1)) as revealed by the targeted deletion of the murine Kir2.1 and Kir2.2 genes.
2001,
Pubmed
Zhu,
Identification of endogenous outward currents in the human embryonic kidney (HEK 293) cell line.
1998,
Pubmed
Zhu,
Effects of intra- and extracellular acidifications on single channel Kir2.3 currents.
1999,
Pubmed
,
Xenbase
