Conductance of Connexin Hemichannels Segregates with the First Transmembrane Segment

Hu, Xiaoyan; Ma, Meiyun; Dahl, Gerhard

doi:10.1529/biophysj.105.066373

Cited by 33 publications

(33 citation statements)

References 47 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Likewise, gating characteristics were also transferred. These data are consistent with mutational studies on chick homologs of Cx46 and Cx50 (Tong and Ebihara, 2006; Tong et al, 2004) as well as chimeric studies that exchanged domains between Cx32 and Cx37 (Hu et al, 2006). Cx43 differs in that truncation of CT or tagging it with EGFP results in loss of V j gating (Bukauskas et al, 2001; Moreno et al, 2002).…”

Section: Discussionsupporting

confidence: 88%

The N-Terminal Half of the Connexin Protein Contains the Core Elements of the Pore and Voltage Gates

2012

View full text Add to dashboard Cite

Connexins form channels with large aqueous pores that mediate fluxes of inorganic ions and biological signaling molecules. Studies aimed at identifying the connexin pore now include a crystal structure that provides details of putative pore-lining residues that need to be verified using independent biophysical approaches. Here we extended our initial cysteine-scanning studies of the TM1/E1 region of Cx46 hemichannels to include TM2 and TM3 transmembrane segments. No evidence of reactivity was observed in either TM2 or TM3 probed with small or large thiol-modifying reagents. Several identified pore residues in E1 of Cx46 have been verified in different Cx isoforms. Use of variety of thiol reagents indicates that the connexin hemichannel pore is large and flexible enough, at least in the extracellular part of the pore funnel, to accommodate uncommonly large side chains. We also find that that gating characteristics are largely determined by the same domains that constitute the pore. These data indicate that biophysical and structural studies are converging towards a view that the N-terminal half of the Cx protein contains the principal components of the pore and gating elements, with NT, TM1 and E1 forming the pore funnel.

show abstract

Section: Discussionsupporting

confidence: 88%

The N-Terminal Half of the Connexin Protein Contains the Core Elements of the Pore and Voltage Gates

2012

View full text Add to dashboard Cite

show abstract

“…As shown previously (23,24,37,39), Cx32E 1 43 induces a nonjunctional membrane conductance, which shares properties with the gap junction channels formed by this connexin chimera. The shared properties include attenuation of channel activity by cytoplasmic acidification.…”

Section: Resultssupporting

confidence: 75%

Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Wang¹,

Ma²,

Locovei³

et al. 2007

American Journal of Physiology-Cell Physiology

Self Cite

181

204

View full text Add to dashboard Cite

. Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters. Am J Physiol Cell Physiol 293: C1112-C1119, 2007. First published July 27, 2007; doi:10.1152/ajpcell.00097.2007.-Connexin mimetic peptides are widely used to assess the contribution of nonjunctional connexin channels in several processes, including ATP release. These peptides are derived from various connexin sequences and have been shown to attenuate processes downstream of the putative channel activity. Yet so far, no documentation of effects of peptides on connexin channels has been presented. We tested several connexin and pannexin mimetic peptides and observed attenuation of channel currents that is not compatible with sequence specific actions of the peptides. Connexin mimetic peptides inhibited pannexin channel currents but not the currents of the channel formed by connexins from which the sequence was derived. Pannexin mimetic peptides did inhibit pannexin channel currents but also the channels formed by connexin 46. The same pattern of effects was observed for dye transfer, except that the inhibition levels were more pronounced than for the currents. The channel inhibition by peptides shares commonalities with channel effects of polyethylene glycol (PEG), suggesting a steric block as a mechanism. PEG accessibility is in the size range expected for the pore of innexin gap junction channels, consistent with a functional relatedness of innexin and pannexin channels.

show abstract

“…Channel unitary conductance, in picoSiemens (pS), being the ease or difficulty with which ions pass through single channels when a voltage is imposed across the channel, are remarkably different for different connexin isoforms (Beblo and Veenstra, 1997; Hu et al, 2006; Moreno et al, 1994a; Moreno et al, 1994b; Puljung et al, 2004; Reed et al, 1993; Valiunas, 2002; Veenstra et al, 1994a; Veenstra et al, 1994b); itself this means the internal pore topography of gap junction channels formed by different connexin isoforms are different. The relative unitary conductance of homotypic channels is in the order; Cx37 (300ps) > Cx40 (140pS) > Cx43 (100pS) > Cx45 (30pS).…”

Section: Permeability Of Vascular Connexin Channelsmentioning

confidence: 99%

Chapter 2 Biological and Biophysical Properties of Vascular Connexin Channels

Johnstone

Isakson

Locke

2009

International Review of Cell and Molecular Biology

View full text Add to dashboard Cite

Intercellular channels formed by connexin proteins play a pivotal role in the direct movement of ions and larger cytoplasmic solutes between vascular endothelial cells, between vascular smooth muscle cells, and between endothelial and smooth muscle cells. Multiple genetic and epigenetic factors modulate connexin expression levels and/or channel function, including cell type-independent and cell type-specific transcription factors, posttranslational modification and localized membrane targeting. Additionally, differences in protein-protein interactions, including those between connexins, significantly contribute to both vascular homeostasis and disease progression. The biophysical properties of the connexin channels identified in the vasculature, those formed by Cx37, Cx40, Cx43 and/or Cx45 proteins, are discussed in this review in the physiological and pathophysiological context of vessel function.

show abstract

Conductance of Connexin Hemichannels Segregates with the First Transmembrane Segment

Cited by 33 publications

References 47 publications

The N-Terminal Half of the Connexin Protein Contains the Core Elements of the Pore and Voltage Gates

The N-Terminal Half of the Connexin Protein Contains the Core Elements of the Pore and Voltage Gates

Modulation of membrane channel currents by gap junction protein mimetic peptides: size matters

Chapter 2 Biological and Biophysical Properties of Vascular Connexin Channels

Contact Info

Product

Resources

About