title: The intercellular synchronization of Ca2+ oscillations evaluates Cx36-dependent coupling.
abstract: Connexin36 (Cx36) plays an important role in insulin secretion by controlling the intercellular synchronization of Ca(2+) transients induced during stimulation. The lack of drugs acting on Cx36 channels is a major limitation in further unraveling the molecular mechanism underlying this effect. To screen for such drugs, we have developed an assay allowing for a semi-automatic, fluorimetric quantification of Ca(2+) transients in large populations of MIN6 cells. Here, we show that (1) compared to control cells, MIN6 cells with reduced Cx36 expression or function showed decreased synchrony of glucose-induced Ca(2+) oscillations; (2) glibenclamide, a sulphonylurea which promotes Cx36 junctions and coupling, increased the number of synchronous MIN6 cells, whereas quinine, an antimalarial drug which inhibits Cx36-dependent coupling, decreased this proportion; (3) several drugs were identified that altered the intercellular Ca(2+) synchronization, cell coupling and distribution of Cx36; (4) some of them also affected insulin content. The data indicate that the intercellular synchronization of Ca(2+) oscillations provides a reliable and non-invasive measurement of Cx36-dependent coupling, which is useful to identify novel drugs affecting the function of β-cells, neurons, and neuron-related cells that express Cx36.
authors: Department of Cell Physiology and Metabolism, University of Geneva School of Medicine, Geneva, Switzerland. sabine@broadinstitute.org
authors: Sabine
authors: S
authors: Bavamian
authors: Helena
authors: H
authors: Pontes
authors: José
authors: J
authors: Cancela
authors: Anne
authors: A
authors: Charollais
authors: Sergei
authors: S
authors: Startchik
authors: Dimitri
authors: D
authors: Van de Ville
authors: Paolo
authors: P
authors: Meda
mesh_terms: D000818:Animals; D000962:Antimalarials / Q000494:pharmacology; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology*; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D017630:Connexins / Q000235:genetics / Q000378:metabolism*; D007328:Insulin / Q000235:genetics / Q000378:metabolism; D000078790:Insulin Secretion; D051379:Mice; D011803:Quinine / Q000494:pharmacology; D000097004:Gap Junction delta-2 Protein
chemical_list: D000962:Antimalarials; D002118:Calcium; D017630:Connexins; D007328:Insulin; D011803:Quinine; D000097004:Gap Junction delta-2 Protein