Gating and regulation of connexin 43 (Cx43) hemichannels

Contreras, Jorge E.; Sáez, Juan C.; Bukauskas, Feliksas F.; Bennett, Michael V. L.

doi:10.1073/pnas.1434298100

Cited by 402 publications

(493 citation statements)

References 41 publications

Supporting

Mentioning

438

Contrasting

Unclassified

Order By: Relevance

“…*P Ͻ 0.05; **P Ͻ 0.01. 7, PEGs attenuated pannexin currents in a size-dependent manner, with peak inhibition obtained with PEG 1500. The level of inhibition of pannexin channel currents by PEG was similar to that observed with the mimetic peptides.…”

Section: Resultsmentioning

confidence: 89%

See 1 more Smart Citation

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

182

205

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

Section: Resultsmentioning

confidence: 89%

“…This type of channel activity is by and large not seen in other expression systems and might not occur in vivo (10,42). Connexon activity by other connexins is usually only observed under extreme conditions, like depolarization to more than ϩ50 mV, and even then the events of channel openings are extremely rare (7).…”

mentioning

confidence: 97%

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

182

205

View full text Add to dashboard Cite

show abstract

“…(Although, as will be discussed, the substate conductances in hemichannels and cell-cell channels are inconsistent; the deviation is similar for five different connexins.) The hemichannels have fastgating transitions between the fully open state and the substate, and slow-gating transitions between the closed state and either the fully open state or substate, as is observed with cell-cell channels [22]. The hemichannels exhibit pharmacology like that of the cell-cell channels.…”

Section: So Are These Really Hemichannel Currents?mentioning

confidence: 85%

New roles for astrocytes: Gap junction hemichannels have something to communicate

Bennett

Contreras

Bukauskas

et al. 2003

Trends in Neurosciences

Self Cite

375

279

View full text Add to dashboard Cite

Gap junctions are clusters of aqueous channels that connect the cytoplasm of adjoining cells. Each cell contributes a hemichannel, or connexon, to each cell-cell channel. The cell-cell channels are permeable to relatively large molecules, and it was thought that opening of hemichannels to the extracellular space would kill cells through loss of metabolites, collapse of ionic gradients and influx of Ca 2+ . Recent findings indicate that specific non-junctional hemichannels do open under both physiological and pathological conditions, and that opening is functional or deleterious depending on the situation. Most of these studies utilized cells in tissue culture that expressed a specific gap junction protein, connexin 43. Several such examples are reviewed here, with a particular focus on astrocytes.Gap junctions mediate intercellular communication by providing ultrastructural cytoplasmic continuity, and they are integral to formation of the functional syncytium of astrocytes. Each of the joined cells contributes a hemichannel or connexon to each cell-cell channel ( Figure 1; Box 1). Each hemichannel comprises a hexamer of connexins arranged around a central pore, and the cell-cell channels are gated by several stimuli, including transjunctional voltage, low pH and various pharmacological agents. Connexins are encoded by a gene family with at least 20 members in mammals [1].Gap-junction pores are nominally 1.0-1.5 nm in diameter and are permeable to molecules of 1 kDa [2]. Junctions formed from connexin 43 (Cx43), the predominant connexin in astrocytes, are permeable to Lucifer Yellow (443 Da, −2 charge) and propidium (420 Da, +2 charge). Other connexins appear to be more charge selective: Cx32 is more permeable to anions and Cx45 is more permeable to cations [2]. Single-channel conductance varies widely, from ~15 pS for Cx36 [3] and 110 pS for Cx43 [4] to ~375 pS for Cx37 [5]. The maximum size of permeant species also varies. Such diversity in selectivity and conductance are likely to account for the expansion of the connexin family. Why shouldn't hemichannels be open?Given the permeability and conductance of gap junctions, and the expectation that an open hemichannel would have twice the conductance and permeability of a cell-cell channel (in terms of ion or molecular flux, rather than selectivity), it was thought unlikely that hemichannels in the non-junctional membrane would open [6]. Direct evidence for this was provided by measurements during formation of the first channel between a newly apposed pair of cells. Each cell was held at a different potential, and then when the first channel NIH-PA Author ManuscriptNIH-PA Author Manuscript NIH-PA Author Manuscript opened, increased current was seen in the cell held at a more positive potential and decreased (more negative) current was seen in the other cell, but the sum of the currents clamping the two cells remained constant [7]. Thus, there was no change in the current flowing into the extracellular space, and the hemichannels were closed before openin...

show abstract

“…One possible explanation is that dialysis of cell contents, which occurs during whole cell patch clamping, may inhibit channel activity. A second possibility is that hemichannel openings are too infrequent or too brief to be resolved by electrophysiologic methods (Contreras et al 2003).…”

Section: Discussionmentioning

confidence: 99%

Human oligodendrocytes express Cx31.3: Function and interactions with Cx32 mutants

Sargiannidou

Ahn

Enriquez

et al. 2008

Neurobiology of Disease

View full text Add to dashboard Cite

Murine oligodendrocytes express the gap junction (GJ) proteins connexin32 (Cx32), Cx47, and Cx29. CNS phenotypes in patients with X-linked Charcot-Marie-Tooth disease may be caused by dominant effects of Cx32 mutations on other connexins. Here we examined the expression of Cx31.3 (the human ortholog of murine Cx29) in human brain and its relation to the other oligodendrocyte GJ proteins Cx32 and Cx47. Furthermore, we investigated in vitro whether Cx32 mutants with CNS manifestations affect the expression and function of Cx31.3. Cx31.3 was localized mostly in the gray matter along small myelinated fibers similar to Cx29 in rodent brain and was coexpressed with Cx32 in a subset of human oligodendrocytes. In HeLa cells Cx31.3 was localized at the cell membrane and appeared to form hemichannels but no GJs. Cx32 mutants with CNS manifestations were retained intracellularly, but did not alter the cellular localization or function of co-expressed Cx31.3. Thus, Cx31.3 shares many characteristics with its ortholog Cx29. Cx32 mutants with CNS phenotypes do not affect the trafficking or function of Cx31.3, and may have other toxic effects in oligodendrocytes.

show abstract

Gating and regulation of connexin 43 (Cx43) hemichannels

Abstract: gap junction ͉ connexon ͉ dye uptake ͉ permeation

Cited by 402 publications

References 41 publications

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

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

New roles for astrocytes: Gap junction hemichannels have something to communicate

Human oligodendrocytes express Cx31.3: Function and interactions with Cx32 mutants

Contact Info

Product

Resources

About