Connexin 43 hemichannels contribute to cytoplasmic Ca2+ oscillations by providing a bimodal Ca2+-dependent Ca2+ entry pathway.

التفاصيل البيبلوغرافية
العنوان:	Connexin 43 hemichannels contribute to cytoplasmic Ca2+ oscillations by providing a bimodal Ca2+-dependent Ca2+ entry pathway.
المؤلفون:	De Bock, Marijke, Wang, Nan, Bol, Mélissa, Decrock, Elke, Ponsaerts, Raf, Bultynck, Geert, Dupont, Geneviève, Leybaert, Luc
المصدر:	The Journal of biological chemistry, 287 (15
سنة النشر:	2012
المجموعة:	DI-fusion : dépôt institutionnel de l'Université libre de Bruxelles (ULB)
مصطلحات موضوعية:	Chimie, Adenosine Triphosphate -- metabolism -- pharmacology, Animals, Bradykinin -- pharmacology, Calcium -- metabolism, Calcium Channel Blockers -- pharmacology, Calcium Channels -- metabolism, Calcium Signaling, Carbenoxolone -- pharmacology, Cell Line, Connexin 43 -- genetics -- metabolism, Connexins -- metabolism, Cytochromes c -- metabolism -- physiology, Cytoplasm -- metabolism, Dogs, Fluoresceins -- metabolism, Gene Knockdown Techniques, Humans, Inositol 1,4,5-Trisphosphate -- metabolism, Oligopeptides -- pharmacology, Peptides -- pharmacology, RNA Interference, Rats, Recombinant Proteins -- metabolism
الوصف:	Many cellular functions are driven by changes in the intracellular Ca(2+) concentration ([Ca(2+)](i)) that are highly organized in time and space. Ca(2+) oscillations are particularly important in this respect and are based on positive and negative [Ca(2+)](i) feedback on inositol 1,4,5-trisphosphate receptors (InsP(3)Rs). Connexin hemichannels are Ca(2+)-permeable plasma membrane channels that are also controlled by [Ca(2+)](i). We aimed to investigate how hemichannels may contribute to Ca(2+) oscillations. Madin-Darby canine kidney cells expressing connexin-32 (Cx32) and Cx43 were exposed to bradykinin (BK) or ATP to induce Ca(2+) oscillations. BK-induced oscillations were rapidly (minutes) and reversibly inhibited by the connexin-mimetic peptides (32)Gap27/(43)Gap26, whereas ATP-induced oscillations were unaffected. Furthermore, these peptides inhibited the BK-triggered release of calcein, a hemichannel-permeable dye. BK-induced oscillations, but not those induced by ATP, were dependent on extracellular Ca(2+). Alleviating the negative feedback of [Ca(2+)](i) on InsP(3)Rs using cytochrome c inhibited BK- and ATP-induced oscillations. Cx32 and Cx43 hemichannels are activated by <500 nm [Ca(2+)](i) but inhibited by higher concentrations and CT9 peptide (last 9 amino acids of the Cx43 C terminus) removes this high [Ca(2+)](i) inhibition. Unlike interfering with the bell-shaped dependence of InsP(3)Rs to [Ca(2+)](i), CT9 peptide prevented BK-induced oscillations but not those triggered by ATP. Collectively, these data indicate that connexin hemichannels contribute to BK-induced oscillations by allowing Ca(2+) entry during the rising phase of the Ca(2+) spikes and by providing an OFF mechanism during the falling phase of the spikes. Hemichannels were not sufficient to ignite oscillations by themselves; however, their contribution was crucial as hemichannel inhibition stopped the oscillations. ; Journal Article ; Research Support, Non-U.S. Gov't ; SCOPUS: ar.j ; info:eu-repo/semantics/published
نوع الوثيقة:	article in journal/newspaper
وصف الملف:	2 full-text file(s): application/pdf \| application/pdf
اللغة:	English
Relation:	uri/info:doi/10.1074/jbc.M111.299610; uri/info:pii/M111.299610; uri/info:pmid/22351781; uri/info:scp/84859491380; uri/info:pmcid/PMC3320976; https://dipot.ulb.ac.be/dspace/bitstream/2013/146309/3/PMC3320976.pdf; https://dipot.ulb.ac.be/dspace/bitstream/2013/146309/5/doi_130214.pdf; http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/146309
الاتاحة:	http://hdl.handle.net/2013/ULB-DIPOT:oai:dipot.ulb.ac.be:2013/146309 https://dipot.ulb.ac.be/dspace/bitstream/2013/146309/3/PMC3320976.pdf https://dipot.ulb.ac.be/dspace/bitstream/2013/146309/5/doi_130214.pdf
رقم الانضمام:	edsbas.FB84267E
قاعدة البيانات:	BASE

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