Long-chain n-alkanols and arachidonic acid interfere with the V m -sensitive gating mechanism of gap junction channels

1997 ◽  
Vol 435 (2) ◽  
pp. 310-319 ◽  
Author(s):  
R. Weingart ◽  
Feliksas F. Bukauskas
Keyword(s):  
Arachidonic Acid ◽  
Gap Junction ◽  
Gap Junction Channels ◽  
Gating Mechanism ◽  
Long Chain

Arachidonic acid closes gap junction channels in rat lacrimal glands

1989 ◽  
Vol 413 (3) ◽  
pp. 273-279 ◽  
Author(s):  
Christian Giaume ◽  
Clotilde Randriamampita ◽  
Alain Trautmann
Keyword(s):  
Arachidonic Acid ◽  
Gap Junction ◽  
Lacrimal Glands ◽  
Gap Junction Channels

scholarly journals Dissection of the Molecular Basis of pp60v-src Induced Gating of Connexin 43 Gap Junction Channels

1999 ◽  
Vol 144 (5) ◽  
pp. 1033-1045 ◽  
Author(s):  
Lan Zhou ◽  
Eileen M. Kasperek ◽  
Bruce J. Nicholson
Keyword(s):  
Map Kinase ◽  
Gap Junction ◽  
Connexin 43 ◽  
Rat Kidney ◽  
Serine Phosphorylation ◽  
K Channel ◽  
Xenopus Laevis Oocyte ◽  
Gap Junction Channels ◽  
Gating Mechanism ◽  
Junctional Communication

Suppression of gap-junctional communication by various protein kinases, growth factors, and oncogenes frequently correlates with enhanced mitogenesis. The oncogene v-src appears to cause acute closure of gap junction channels. Tyr265 in the COOH-terminal tail of connexin 43 (Cx43) has been implicated as a potential target of v-src, although v-src action has also been associated with changes in serine phosphorylation. We have investigated the mechanism of this acute regulation through mutagenesis of Cx43 expressed in Xenopus laevis oocyte pairs. Truncations of the COOH-terminal domain led to an almost complete loss of response of Cx43 to v-src, but this was restored by coexpression of the independent COOH-terminal polypeptide. This suggests a ball and chain gating mechanism, similar to the mechanism proposed for pH gating of Cx43, and K+ channel inactivation. Surprisingly, we found that v-src mediated gating of Cx43 did not require the tyrosine site, but did seem to depend on the presence of two potential SH3 binding domains and the mitogen-activated protein (MAP) kinase phosphorylation sites within them. Further point mutagenesis and pharmacological studies in normal rat kidney (NRK) cells implicated MAP kinase in the gating response to v-src, while the stable binding of v-src to Cx43 (in part mediated by SH3 domains) did not correlate with its ability to mediate channel closure. This suggests a common link between closure of gap junctions by v-src and other mitogens, such as EGF and lysophosphatidic acid (LPA).

scholarly journals Regulation of connexin36 gap junction channels byn-alkanols and arachidonic acid

2013 ◽  
Vol 591 (8) ◽  
pp. 2087-2101 ◽  
Author(s):  
Alina Marandykina ◽  
Nicolás Palacios-Prado ◽  
Lina Rimkutė ◽  
Vytenis A. Skeberdis ◽  
Feliksas F. Bukauskas
Keyword(s):  
Arachidonic Acid ◽  
Gap Junction ◽  
Gap Junction Channels

scholarly journals The Effect of Arachidonic Acid on Junctional Conductance and Gating of Connexin 36 Gap Junction Channels and their Modulation by N-Alkanols

2013 ◽  
Vol 104 (2) ◽  
pp. 632a
Author(s):  
Alina Marandykina ◽  
Lina Rimkutė ◽  
Nicolás Palacios-Prado ◽  
Arvydas Skeberdis ◽  
Feliksas Bukauskas
Keyword(s):  
Arachidonic Acid ◽  
Gap Junction ◽  
Gap Junction Channels ◽  
Connexin 36 ◽  
Junctional Conductance

scholarly journals Conductance and Permeability of the Residual State of Connexin43 Gap Junction Channels

2002 ◽  
Vol 119 (2) ◽  
pp. 171-186 ◽  
Author(s):  
Feliksas F. Bukauskas ◽  
Angele Bukauskiene ◽  
Vytas K. Verselis
Keyword(s):  
Gap Junction ◽  
Fluorescent Protein ◽  
Single Channel ◽  
Electrical Coupling ◽  
Dye Transfer ◽  
Channel Pore ◽  
Gap Junction Channels ◽  
Gating Mechanism ◽  
Gated Channel ◽  
Green Fluorescent

We used cell lines expressing wild-type connexin43 and connexin43 fused with the enhanced green fluorescent protein (Cx43-EGFP) to examine conductance and perm-selectivity of the residual state of Cx43 homotypic and Cx43/Cx43-EGFP heterotypic gap junction channels. Each hemichannel in Cx43 cell–cell channel possesses two gates: a fast gate that closes channels to the residual state and a slow gate that fully closes channels; the transjunctional voltage (Vj) closes the fast gate in the hemichannel that is on the relatively negative side. Here, we demonstrate macroscopically and at the single-channel level that the I-V relationship of the residual state rectifies, exhibiting higher conductance at higher Vjs that are negative on the side of gated hemichannel. The degree of rectification increases when Cl− is replaced by Asp− and decreases when K+ is replaced by TEA+. These data are consistent with an increased anionic selectivity of the residual state. The Vj-gated channel is not permeable to monovalent positively and negatively charged dyes, which are readily permeable through the fully open channel. These data indicate that a narrowing of the channel pore accompanies gating to the residual state. We suggest that the fast gate operates through a conformational change that introduces positive charge at the cytoplasmic vestibule of the gated hemichannel, thereby producing current rectification, increased anionic selectivity, and a narrowing of channel pore that is largely responsible for reducing channel conductance and restricting dye transfer. Consequently, the fast Vj-sensitive gating mechanism can serve as a selectivity filter, which allows electrical coupling but limits metabolic communication.

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