Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1

Pessia, Mauro; Imbrici, Paola; D’Adamo, Maria Cristina; Salvatore, Lorena; Tucker, Stephen J.

doi:10.1111/j.1469-7793.2001.0359f.x

Cited by 113 publications

(146 citation statements)

References 17 publications

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“…This result differs from the observation that Kir4.2 expressed in oocytes was consistently inhibited by reduced pH with a pK a of 6.7 in whole cell and 7.1 in excised, inside-out patches (22), and greatly reduces the probability that the apical Kir channel is a homomeric form of Kir4.2. The difference of ϳ0.4 pH units between pK a values we measured in the different patch configurations, and the absence of any pH sensitivity in half of the channels we tested further suggests that Kir pH sensitivity depends upon additional components or states of the channel.…”

Section: Modulation Of Apical Kir By Internal Phcontrasting

confidence: 98%

“…Among them, heteromeric Kir4.1-Kir5.1 is drastically shifted in pH sensitivity relative to homomeric Kir4.1, from 6.0 to pK a 7.45 (20). On the other hand, heteromeric Kir4.2-Kir5.1 channels had only mildly shifted pH sensitivity from pK a 7.07 to 7.35 (22). The presence of any heteromeric Kir-Kir5.1 channels in Calu-3 has been negated by our RT-PCR analysis.…”

Section: )mentioning

confidence: 97%

“…Unitary Conductance-The unitary conductance of 24.4 pS in the inward direction (␥ in ) differs significantly from unitary conductances for all Kir channels except Kir2.1 (␥ in ϭ 24 or 26.9 pS) (16,17), Kir4.1 (␥ in ϭ 22.8 -27.2 pS) (18 -21), and Kir4.2 (␥ in ϭ 25.2 pS) (22).…”

Section: Comparison Of the Apical K ϩ Channel Properties With Prior Dmentioning

confidence: 99%

“…Lysates-RT-PCR was performed to amplify transcripts of Kir4.1 and 4.2; in addition we looked for Kir5.1, which is capable of forming heteromultimers when co-expressed with Kir4.1 (21,25) or Kir4.2 (22,26). Evidence was obtained for expression of Kir4.2, but not for Kir4.1 or Kir5.1.…”

Section: Expression Of Kir42 Transcripts In Calu-3mentioning

confidence: 99%

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An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

Krouse

Joo

et al. 2004

Journal of Biological Chemistry

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Patch clamp methods and reverse transcription-polymerase chain reaction (RT-PCR) were used to characterize an apical K ؉ channel in Calu-3 cells, a widely used model of human airway gland serous cells. In cell-attached and excised apical membrane patches, we found an inwardly rectifying K ؉ channel (Kir). The permeability ratio was P Na /P K ‫؍‬ 0.058. In 30 patches with both cystic fibrosis transmembrane conductance regulator and Kir present, we observed 79 cystic fibrosis transmembrane conductance regulator and 58 Kir channels. The average chord conductance was 24.4 ؎ 0.5 pS (n ‫؍‬ 11), between 0 and ؊200 mV, and was 9.6 ؎ 0.7 pS (n ‫؍‬ 8), between 0 and 50 mV; these magnitudes and their ratio of ϳ2.5 are most similar to values for rectifying K ؉ channels of the Kir4.x subfamilies. We attempted to amplify transcripts for Kir4.1, Kir4.2, and Kir5.1; of these only Kir4.2 was present in Calu-3 lysates. The channel was only weakly activated by ATP and was relatively insensitive to internal pH. External Cs ؉ and Ba 2؉ blocked the channel with K d values in the millimolar range. Quantitative modeling of Cl ؊ secreting epithelia suggests that secretion rates will be highest and luminal K ؉ will rise to 16 -28 mM if 11-25% of the total cellular K ؉ conductance is placed in the apical membrane (Cook, D. I., and Young, J. A. (1989) J. Membr. Biol. 110, 139 -146). Thus, we hypothesize that the K ؉ channel described here optimizes the rate of secretion and is involved in K ؉ recycling for the recently proposed apical H ؉ -K ؉ -ATPase in Calu-3 cells.

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Section: Modulation Of Apical Kir By Internal Phcontrasting

confidence: 98%

Section: )mentioning

confidence: 97%

Section: Comparison Of the Apical K ϩ Channel Properties With Prior Dmentioning

confidence: 99%

Section: Expression Of Kir42 Transcripts In Calu-3mentioning

confidence: 99%

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An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

Krouse

Joo

et al. 2004

Journal of Biological Chemistry

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“…5A). These channels have in common that they are gated by intracellular protons (3)(4)(5)(6)26). We chose Kir1.1 to study the role of the position Ile-63 that corresponds to Arg-54 in Kir6.2.…”

Section: Arg-54 In the N Terminus Of Kir62 Is A Major Determinant Fomentioning

confidence: 99%

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

Schulze¹,

Krauter²,

Fritzenschaft

et al. 2003

Journal of Biological Chemistry

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Phosphatidylinositol polyphosphates (PIPs) are potent modulators of Kir channels. Previous studies have implicated basic residues in the C terminus of Kir6.2 channels as interaction sites for the PIPs. Here we examined the role of the N terminus and identified an arginine (Arg-54) as a major determinant for PIP 2 modulation of ATP sensitivity in K ATP channels. Mutation of Arg-54 to the neutral glutamine (R54Q) and, in particular, to the negatively charged glutamate (R54E) impaired PIP 2 modulation of ATP inhibition, while mutation to lysine (R54K) had no effect. These data suggest that electrostatic interactions between PIP 2 and Arg-54 are an essential step for the modulation of ATP sensitivity. This N-terminal PIP 2 site is highly conserved in Kir channels with the exception of the pH-gated channels Kir1.1, Kir4.1, and Kir5.1 that contain a neutral residue at the corresponding positions. Introduction of an arginine at this position in Kir1.1 channels rendered the N-terminal PIP 2 site functional largely increasing the PIP 2 affinity. Moreover, Kir1.1 channels lose the ability to respond to physiological changes of the intracellular pH. These results explain the need of a silent N-terminal PIP 2 site in pH-gated channels and highlight the N terminus as an important region for PIP 2 modulation of Kir channel gating.Kir channels are a superfamily of eukaryotic channel proteins that are expressed in many tissues and responsible for important physiological processes such as cell excitability, insulin secretion, K ϩ homeostasis, vascular tone, and regulation of the heart rate. Four subunits assemble to a channel. Each subunit contains two transmembrane segments with cytoplasmic N-and C-terminal domains and a connecting loop forming the pore (1). Some members of the Kir channel family are endowed with gating mechanisms such as ATP gating (K ATP channels) (2) and pH gating (Kir1.1 and Kir4.1 channels) (3). These gating mechanisms are central for the diverse functions of Kir channels in physiology and the understanding of the related pathophysiology. Kir1, Kir4, and Kir5 channels, that are predominantly expressed in epithelia, are exquisitely sensitive to changes in intracellular pH in the physiological range (3-5). This pH sensitivity is mediated by the protonation of a lysine in the N terminus (Lys-80 in Kir1.1) that induces closure of the channel's pore by an allosteric mechanism (pH gating) (3, 6). Even small changes in the pH sensitivity can cause severe kidney defects such as the Bartter syndrome (3), highlighting the physiological importance of proper pH gating in Kir1.1 channels. Kir6 channels display a very ubiquitous expression pattern and, in coassembly with the sulfonylurea receptor (SUR), 1 represent the ATP-sensitive K ϩ channels (K ATP channels) (7). Intracellular ATP closes K ATP channels by binding to the Kir6.2 subunits (ATP gating), whereas the SURs act as regulatory subunits endowing the channel with sensitivity to MgADP and pharmacological compounds. The ATP/ADP dependence of K ATP channels couple...

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K ⁺ Channels: Function‐Structural Overview

González

Báez-Nieto

Valencia

et al. 2012

Comprehensive Physiology

189

139

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Potassium channels are particularly important in determining the shape and duration of the action potential, controlling the membrane potential, modulating hormone secretion, epithelial function and, in the case of those K + channels activated by Ca 2+ , damping excitatory signals. The multiplicity of roles played by K + channels is only possible to their mammoth diversity that includes at present 70 K + channels encoding genes in mammals. Today, thanks to the use of cloning, mutagenesis, and the more recent structural studies using x‐ray crystallography, we are in a unique position to understand the origins of the enormous diversity of this superfamily of ion channels, the roles they play in different cell types, and the relations that exist between structure and function. With the exception of two‐pore K + channels that are dimers, voltage‐dependent K + channels are tetrameric assemblies and share an extremely well conserved pore region, in which the ion‐selectivity filter resides. In the present overview, we discuss in the function, localization, and the relations between function and structure of the five different subfamilies of K + channels: (a) inward rectifiers, Kir; (b) four transmembrane segments‐2 pores, K 2P ; (c) voltage‐gated, Kv; (d) the Slo family; and (e) Ca 2+ ‐activated SK family, SKCa. © 2012 American Physiological Society. Compr Physiol 2:2087‐2149, 2012.

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Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1

Cited by 113 publications

References 17 publications

An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

K ⁺ Channels: Function‐Structural Overview

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Differential pH sensitivity of Kir4.1 and Kir4.2 potassium channels and their modulation by heteropolymerisation with Kir5.1

Cited by 113 publications

References 17 publications

An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

An Inwardly Rectifying Potassium Channel in Apical Membrane of Calu-3 Cells

Phosphatidylinositol 4,5-Bisphosphate (PIP2) Modulation of ATP and pH Sensitivity in Kir Channels

K + Channels: Function‐Structural Overview

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K ⁺ Channels: Function‐Structural Overview