کد مقاله کد نشریه سال انتشار مقاله انگلیسی نسخه تمام متن
2923724 1175884 2009 7 صفحه PDF دانلود رایگان
عنوان انگلیسی مقاله ISI
Phosphorylation of connexin43 on serine 306 regulates electrical coupling
موضوعات مرتبط
علوم پزشکی و سلامت پزشکی و دندانپزشکی کاردیولوژی و پزشکی قلب و عروق
پیش نمایش صفحه اول مقاله
Phosphorylation of connexin43 on serine 306 regulates electrical coupling
چکیده انگلیسی

BackgroundPhosphorylation is a key regulatory event in controlling the function of the cardiac gap junction protein connexin43 (Cx43). Three new phosphorylation sites (S296, S297, S306) have been identified on Cx43; two of these sites (S297 and S306) are dephosphorylated during ischemia. The functional significance of these new sites is currently unknown.ObjectiveThe purpose of this study was to examine the role of S296, S297, and S306 in the regulation of electrical intercellular communication.MethodsTo mimic constitutive dephosphorylation, serine was mutated to alanine at the three sites and expressed in HeLa cells. Electrical coupling and single channel measurements were performed by double patch clamp. Protein expression levels were assayed by western blotting, localization of Cx43, and phosphorylation of S306 by immunolabeling. Free hemichannels were assessed by biotinylation.ResultsMacroscopic conductance in cells expressing S306A was reduced to 57% compared to wild type (WT), whereas coupling was not significantly changed in cells expressing either S296A or S297A. S306A-expressing cells displayed similar protein and free hemichannel abundance compared to WT Cx43, whereas the fractional area of plaques in cell-to-cell interfaces was increased. However, single channel measurements showed a WT Cx43 main state conductance of 119 pS, whereas the main state conductance of S306A channels was reduced to 95 pS. Furthermore, channel gating was affected in S306A channels.ConclusionLack of phosphorylation at serine 306 results in reduced coupling, which can be explained by reduced single channel conductance. We suggest that dephosphorylation of S306 partly explains the electrical uncoupling seen in myocardial ischemia.

ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Heart Rhythm - Volume 6, Issue 11, November 2009, Pages 1632–1638
نویسندگان
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