Osteoclast spreading kinetics are correlated with an oscillatory activation of a calcium-dependent potassium current.
Cell movement and spreading involve calcium-dependent processes and ionic channel activation. During bone resorption, osteoclasts alternate between spread, motile and resorptive phases. We investigated whether the electrical membrane properties of osteoclasts were linked to their membrane morphological changes. Rabbit osteoclasts were recorded by time-lapse videomicroscopy performed simultaneously with patch-clamp whole cell and single channel recordings. Original image analysis methods were developed and used to demonstrate for the first time an oscillatory activation of a spontaneous membrane current in osteoclasts, which is directly correlated to the membrane movement rate. This current was identified as a calcium-dependent potassium current (IK(Ca)) that is sensitive to both charybdotoxin and apamin and was generated by a channel with unitary conductance of approximately 25+/-2 pS. Blockade of this current also decreased osteoclast spreading and inhibited bone resorption in vitro, demonstrating a physiological role for this current in osteoclast activity. These results establish for the first time a temporal correlation between lamellipodia formation kinetics and spontaneous peaks of IK(Ca), which are both involved in the control of osteoclast spreading and bone resorption.
Espinosa
Leon
L
INSERM Unit 403, Hôpital E Herriot, Pavillon F, 69437 Lyon Cedex 03, France.
Paret
Laurent
L
Ojeda
Carlos
C
Tourneur
Yves
Y
Delmas
Pierre D
PD
Chenu
Chantal
C
D000818:Animals; D001683:Biological Clocks / Q000187:drug effects / Q000502:physiology; D001862:Bone Resorption / Q000378:metabolism*; D002118:Calcium / Q000378:metabolism; D020013:Calcium Signaling / Q000187:drug effects / Q000502:physiology*; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism*; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D007700:Kinetics; D010010:Osteoclasts / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects / Q000378:metabolism*; D011554:Pseudopodia / Q000187:drug effects / Q000378:metabolism*; D011817:Rabbits; D014688:Venoms / Q000494:pharmacology
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D014688:Venoms; D011188:Potassium; D002118:Calcium