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This Article Full Text Full Text (PDF) All Versions of this Article: 291/5/F1045    most recent 00344.2005v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (4) Citing Articles via Google Scholar Google Scholar Articles by Hills, C. E. Articles by Squires, P. E. Search for Related Content PubMed PubMed Citation Articles by Hills, C. E. Articles by Squires, P. E.

Glucose-evoked alterations in connexin43-mediated cell-to-cell communication in human collecting duct: a possible role in diabetic nephropathy

¹Molecular Physiology, Biomedical Research Institute, Department of Biological Sciences, University of Warwick, Coventry, United Kingdom; and ²Unité Institut National de la Santé et de la Recherche Médicale, Universite de Paris, Hôpital Tenon (Assistance Publique-Hôpitaux de Paris), Paris, France

Submitted 23 August 2005 ; accepted in final form 2 May 2006

Aberrant sodium absorption has been linked to the development of hypertension in both renal disease and diabetes. Efficient absorption depends on coordination of cellular activity across the entire epithelium via cell-to-cell coupling. In the current study we have utilized a model human collecting duct cell line (HCD) to assess the role of connexin43 (Cx43)-mediated gap junctions in the transfer of intracellular Ca²⁺ transients within coupled cell clusters. HCD cells express Cx43 mRNA and protein, as well as that for the mechanosensitive transient receptor potential receptor (TRPV4). Mechanical stimulation of individual cells within a cluster evoked a transient rise in cytosolic Ca²⁺ concentration ([Ca²⁺]_i) that propagated between cells via a heptanol-sensitive mechanism. The rise in [Ca²⁺]_i was dependent on both store release and Ca²⁺-influx pathways. Lucifer yellow dye transfer and Cx43 knockdown experiments confirmed direct cell-to-cell communication. Application of the Ca²⁺ ionophore ionomycin, or an increase in glucose (5 to 25 mM), produced a time-dependent (48 h) increase in Cx43 protein expression. The transmission rate of touch-evoked Ca²⁺ transients between coupled cells was accelerated after exposure to high glucose, providing a functional correlate to increased Cx43 expression. These data suggest a pivotal role for Cx43-mediated gap junctions in the synchronization of activity between HCD cells in response to stimuli that mimic osmotic and physical changes. Cx43 expression and cell-to-cell communication increased in response to high glucose and may protect the collecting duct from renal damage associated with more established diabetic nephropathy.

gap junctions

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