Social Networking Among Voltage-Activated Potassium Channels

Brueggemann, Lioubov I.; Gentile, Sandro; Byron, Kenneth L.

doi:10.1016/b978-0-12-386931-9.00010-6

Cited by 8 publications

(6 citation statements)

References 148 publications

(208 reference statements)

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“…The intramolecular docking mechanism we propose for Ca V 2 is reminiscent of the role of the tetramerization domain (T1 domain) in the N-termini of Kv1–Kv4 potassium channels, which has been shown to be involved with the folding and oligomerization of the channels ( Brueggemann et al, 2013 ). Oligomerization requires a threshold level of folding of the N-terminus and it has been suggested that this coupling between folding and assembly of Kv channels may be a common trait ( Robinson and Deutsch, 2005 ).…”

Section: Discussionmentioning

confidence: 99%

A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant

Dahimène

Page

Nieto-Rostro

et al. 2016

Neurobiology of Disease

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Episodic ataxia 2 (EA2) is an autosomal dominant disorder caused by mutations in the gene CACNA1A that encodes the pore-forming CaV2.1 calcium channel subunit. The majority of EA2 mutations reported so far are nonsense or deletion/insertion mutations predicted to form truncated proteins. Heterologous expression of wild-type CaV2.1, together with truncated constructs that mimic EA2 mutants, significantly suppressed wild-type calcium channel function, indicating that the truncated protein produces a dominant-negative effect (Jouvenceau et al., 2001; Page et al., 2004). A similar finding has been shown for CaV2.2 (Raghib et al., 2001). We show here that a highly conserved sequence in the cytoplasmic N-terminus is involved in this process, for both CaV2.1 and CaV2.2 channels. Additionally, we were able to interfere with the suppressive effect of an EA2 construct by mutating key N-terminal residues within it. We postulate that the N-terminus of the truncated channel plays an essential part in its interaction with the full-length CaV2.1, which prevents the correct folding of the wild-type channel. In agreement with this, we were able to disrupt the interaction between EA2 and the full length channel by co-expressing a free N-terminal peptide.

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Section: Discussionmentioning

confidence: 99%

A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant

Dahimène

Page

Nieto-Rostro

et al. 2016

Neurobiology of Disease

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“…In most channels “α-subunits” form the pore for the passage of ions. Attached to the α-subunits are in most cases a variety of other proteins—called auxiliary subunits (β, γ, ε, δ) [ 5 ], or special channel specific proteins, and/or enzymes, such as kinases, phosphatases or heme [ 5 , 6 ]. To classify ion channels by their mechanism of activation (gating) has been considered as a proper means.…”

Section: Ca 2+ -Activated K + mentioning

confidence: 99%

Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels

2015

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All cells contain ion channels in their outer (plasma) and inner (organelle) membranes. Ion channels, similar to other proteins, are targets of oxidative impact, which modulates ion fluxes across membranes. Subsequently, these ion currents affect electrical excitability, such as action potential discharge (in neurons, muscle, and receptor cells), alteration of the membrane resting potential, synaptic transmission, hormone secretion, muscle contraction or coordination of the cell cycle. In this chapter we summarize effects of oxidative stress and redox mechanisms on some ion channels, in particular on maxi calcium-activated potassium (BK) channels which play an outstanding role in a plethora of physiological and pathophysiological functions in almost all cells and tissues. We first elaborate on some general features of ion channel structure and function and then summarize effects of oxidative alterations of ion channels and their functional consequences.

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“…The pore-forming structures of many types of ion channels are thought to form as oligomeric assemblies of α-subunits, with Kv channels forming as tetramers of α-subunits (Catterall, 1988;Brueggemann et al, 2013). The Kv α-subunit proteins are encoded by individual genes in the cell, enabling multiple gene products to assemble in a variety of combinations.…”

Section: Concatenated α-Subunits As a Model To Study Kv Channel Strucmentioning

confidence: 99%

Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 α-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents

2020

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Smooth muscle cells of the vasculature, viscera, and lungs generally express multiple α-subunits of the Kv7 voltage-gated potassium channel family, with increasing evidence that both Kv7.4 and Kv7.5 can conduct "M-currents" that are functionally important for the regulation of smooth muscle contractility. Although expression systems demonstrate that functional channels can form as homomeric tetramers of either Kv7.4 or Kv7.5 α-subunits, there is evidence that heteromeric channel complexes, containing some combination of Kv7.4 and Kv7.5 α-subunits, may represent the predominant configuration natively expressed in some arterial myocytes, such as rat mesenteric artery smooth muscle cells (MASMCs). Our previous work has suggested that Kv7.4/Kv7.5 heteromers can be distinguished from Kv7.4 or Kv7.5 homomers based on their biophysical, regulatory, and pharmacological characteristics, but it remains to be determined how Kv7.4 and Kv7.5 α-subunits combine to produce these distinct characteristics. In the present study, we constructed concatenated dimers or tetramers of Kv7.4 and Kv7.5 α-subunits and expressed them in a smooth muscle cell line to determine if a particular α-subunit configuration can exhibit the features previously reported for natively expressed Kv7 currents in MASMCs. Several unique characteristics of native smooth muscle M-currents were reproduced under conditions that constrain channel formation to a Kv7.4:Kv7.5 stoichiometry of 2:2, with alternating Kv7.4 and Kv7.5 α-subunits within a tetrameric structure. Although other subunit arrangements/combinations are not ruled out, the findings provide new insights into the oligomerization of α-subunits and the ways in which Kv7.4/Kv7.5 subunit assembly can affect smooth muscle signal transduction and pharmacological responses to Kv7 channel modulating drugs.

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Social Networking Among Voltage-Activated Potassium Channels

Cited by 8 publications

References 148 publications

A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant

A CaV2.1 N-terminal fragment relieves the dominant-negative inhibition by an Episodic ataxia 2 mutant

Oxidative Stress and Maxi Calcium-Activated Potassium (BK) Channels

Heteromeric Channels Formed From Alternating Kv7.4 and Kv7.5 α-Subunits Display Biophysical, Regulatory, and Pharmacological Characteristics of Smooth Muscle M-Currents

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