Activation of L-type calcium channels is required for gap junction-mediated intercellular calcium signaling in osteoblastic cells.
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.
Jørgensen
Niklas Rye
NR
Osteoporosis and Metabolic Bone Unit, Department of Endocrinology, Copenhagen University Hospitals, Copenhagen Hospital Corporation DK-2650 Hvidovre, Denmark. niklas@dadlnet.dk
Teilmann
Stefan Cuoni
SC
Henriksen
Zanne
Z
Civitelli
Roberto
R
Sørensen
Ole Helmer
OH
Steinberg
Thomas H
TH
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
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D009543:Nifedipine