Deep Domain Insertion Profiling is a Window into Inward Rectifier K+ Channel Dynamics and Gating

Pancreatic ATP-sensitive K+ channels (KATP) comprise four inward rectifier subunits (Kir6.2), each associated with a sulphonylurea receptor (SUR1). ATP/ADP binding to Kir6.2 shuts KATP. Mg-nucleotide binding to SUR1 stimulates KATP. In the absence of Mg2+, SUR1 increases the apparent affinity for nucleotide inhibition at Kir6.2 by an unknown mechanism. We simultaneously measured channel currents and nucleotide binding to Kir6.2. Fits to combined data sets suggest that KATP closes with only one nucleotide molecule bound. A Kir6.2 mutation (C166S) that increases channel activity did not affect nucleotide binding, but greatly perturbed the ability of bound nucleotide to inhibit KATP. Mutations at position K205 in SUR1 affected both nucleotide affinity and the ability of bound nucleotide to inhibit KATP. This suggests a dual role for SUR1 in KATP inhibition, both in directly contributing to nucleotide binding and in stabilising the nucleotide-bound closed state.

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Primary structure and functional expression of a mouse inward rectifier K+ channel and a rat G-protein-coupled muscarinic K+ channel.

Seibutsu Butsuri ◽

10.2142/biophys.36.270 ◽

1996 ◽

Vol 36 (6) ◽

pp. 270-274

Author(s):

Yoshihiro KUBO

Keyword(s):

G Protein ◽

Primary Structure ◽

Functional Expression ◽

Inward Rectifier ◽

K Channel ◽

G Protein Coupled

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Functional expression of a vertebrate inwardly rectifying K+ channel in yeast.

Molecular Biology of the Cell ◽

10.1091/mbc.6.9.1231 ◽

1995 ◽

Vol 6 (9) ◽

pp. 1231-1240 ◽

Cited By ~ 51

Author(s):

W Tang ◽

A Ruknudin ◽

W P Yang ◽

S Y Shaw ◽

A Knickerbocker ◽

...

Keyword(s):

Transcriptional Control ◽

Xenopus Oocytes ◽

Genetic System ◽

Functional Expression ◽

Inward Rectifier ◽

K Channel ◽

Coding Region ◽

Low Potassium ◽

K Current ◽

Inwardly Rectifying

We describe the expression of gpIRK1, an inwardly rectifying K+ channel obtained from guinea pig cardiac cDNA. gpIRK1 is a homologue of the mouse IRK1 channel identified in macrophage cells. Expression of gpIRK1 in Xenopus oocytes produces inwardly rectifying K+ current, similar to the cardiac inward rectifier current IK1. This current is blocked by external Ba2+ and Cs+. Plasmids containing the gpIRK1 coding region under the transcriptional control of constitutive (PGK) or inducible (GAL) promoters were constructed for expression in Saccharomyces cerevisiae. Several observations suggest that gpIRK1 forms functional ion channels when expressed in yeast. gpIRK1 complements a trk1 delta trk2 delta strain, which is defective in potassium uptake. Expression of gpIRK1 in this mutant restores growth on low potassium media. Growth dependent on gpIRK1 is inhibited by external Cs+. The strain expressing gpIRK1 provides a versatile genetic system for studying the assembly and composition of inwardly rectifying K+ channels.

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Estrogen ameliorates microglial activation by inhibiting the Kir2.1 inward-rectifier K+ channel

Scientific Reports ◽

10.1038/srep22864 ◽

2016 ◽

Vol 6 (1) ◽

Cited By ~ 16

Author(s):

Shih-Ying Wu ◽

Yun-Wen Chen ◽

Sheng-Feng Tsai ◽

Sheng-Nan Wu ◽

Yao-Hsiang Shih ◽

...

Keyword(s):

Microglial Activation ◽

Inward Rectifier ◽

K Channel

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Lysophosphatidylcholine decreases single channel conductance of inward rectifier K channel in mammalian ventricular myocytes.

The Japanese Journal of Physiology ◽

10.2170/jjphysiol.34.369 ◽

1984 ◽

Vol 34 (2) ◽

pp. 369-373 ◽

Cited By ~ 7

Author(s):

Tatsuto KIYOSUE ◽

Masahiro AOMINE ◽

Makoto ARITA

Keyword(s):

Single Channel ◽

Ventricular Myocytes ◽

Inward Rectifier ◽

K Channel ◽

Channel Conductance ◽

Single Channel Conductance

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Subthreshold K+ Channel Dynamics Interact With Stimulus Spectrum to Influence Temporal Coding in an Auditory Brain Stem Model

Journal of Neurophysiology ◽

10.1152/jn.00326.2007 ◽

2008 ◽

Vol 99 (2) ◽

pp. 534-544 ◽

Cited By ~ 15

Author(s):

Mitchell L. Day ◽

Brent Doiron ◽

John Rinzel

Keyword(s):

Brain Stem ◽

Pattern Classification ◽

Power Spectra ◽

Temporal Coding ◽

K Channel ◽

Temporal Precision ◽

Channel Dynamics ◽

Auditory Brain Stem ◽

Low Pass ◽

Temporal Encoding

Neurons in the auditory brain stem encode signals with exceptional temporal precision. A low-threshold potassium current, IKLT, present in many auditory brain stem structures and thought to enhance temporal encoding, facilitates spike selection of rapid input current transients through an associated dynamic gate. Whether the dynamic nature of IKLT interacts with the timescales in spectrally rich input to influence spike encoding remains unclear. We examine the general influence of IKLT on spike encoding of stochastic stimuli using a pattern classification analysis between spike responses from a ventral cochlear nucleus (VCN) model containing IKLT, and the same model with the IKLT dynamics removed. The influence of IKLT on spike encoding depended on the spectral content of the current stimulus such that maximal IKLT influence occurred for stimuli with power concentrated at frequencies low enough (<500 Hz) to allow IKLT activation. Further, broadband stimuli significantly decreased the influence of IKLT on spike encoding, suggesting that broadband stimuli are not well suited for investigating the influence of some dynamic membrane nonlinearities. Finally, pattern classification on spike responses was performed for physiologically realistic conductance stimuli created from various sounds filtered through an auditory nerve (AN) model. Regardless of the sound, the synaptic input arriving at VCN had similar low-pass power spectra, which led to a large influence of IKLT on spike encoding, suggesting that the subthreshold dynamics of IKLT plays a significant role in shaping the response of real auditory brain stem neurons.

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