title: Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells.
abstract: The propagation of mechanically induced intercellular calcium waves (ICW) among osteoblastic cells occurs both by activation of P2Y (purinergic) receptors by extracellular nucleotides, resulting in "fast" ICW, and by gap junctional communication in cells that express connexin43 (Cx43), resulting in "slow" ICW. Human osteoblastic cells transmit intercellular calcium signals by both of these mechanisms. In the current studies we have examined the mechanism of slow gap junction-dependent ICW in osteoblastic cells. In ROS rat osteoblastic cells, gap junction-dependent ICW were inhibited by removal of extracellular calcium, plasma membrane depolarization by high extracellular potassium, and the L-type voltage-operated calcium channel inhibitor, nifedipine. In contrast, all these treatments enhanced the spread of P2 receptor-mediated ICW in UMR rat osteoblastic cells. Using UMR cells transfected to express Cx43 (UMR/Cx43) we confirmed that nifedipine sensitivity of ICW required Cx43 expression. In human osteoblastic cells, gap junction-dependent ICW also required activation of L-type calcium channels and influx of extracellular calcium.
authors.affiliation: Osteoporosis and Metabolic Bone Unit, Department of Endocrinology, Copenhagen University Hospitals, Copenhagen Hospital Corporation DK-2650 Hvidovre, Denmark. niklas@dadlnet.dk
authors.forename: Niklas Rye
authors.initials: NR
authors.lastname: Jørgensen
authors.forename: Stefan Cuoni
authors.initials: SC
authors.lastname: Teilmann
authors.forename: Zanne
authors.initials: Z
authors.lastname: Henriksen
authors.forename: Roberto
authors.initials: R
authors.lastname: Civitelli
authors.forename: Ole Helmer
authors.initials: OH
authors.lastname: Sørensen
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Steinberg
mesh_terms: D000818:Animals; D002121:Calcium Channel Blockers / Q000494:pharmacology; D020746:Calcium Channels, L-Type / Q000378:metabolism* / Q000502:physiology; D020013:Calcium Signaling / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000378:metabolism; D017629:Gap Junctions / Q000378:metabolism* / Q000502:physiology; D006801:Humans; D017136:Ion Transport; D008564:Membrane Potentials / Q000187:drug effects; D009543:Nifedipine / Q000494:pharmacology; D010006:Osteoblasts / Q000166:cytology / Q000378:metabolism*; D051381:Rats
chemical_list: D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine