Volume regulatory decrease in UMR-106.01 cells is mediated by specific alpha1 subunits of L-type calcium channels.
An early cellular response of osteoblasts to swelling is plasma membrane depolarization, accompanied by a transient increase in intracellular calcium ([Ca2+]i), which initiates regulatory volume decrease (RVD). The authors have previously demonstrated a hypotonically induced depolarization of the osteoblast plasma membrane, sufficient to open L-type Ca channels and mediate Ca2+ influx. Herein is described the initiation of RVD in UMR-106.01 cells, mediated by hypotonically induced [Ca2+]i transients resulting from the activation of specific isoforms of L-type Ca channels. The authors further demonstrate that substrate interaction determines which specific alpha1 Ca channel subunit isoform predominates and mediates Ca2+ entry and RVD. Swelling-induced [Ca2+]i transients, and RVD in cells grown on a type I collagen matrix, are inhibited by removal of Ca from extracellular solutions, dihydropyridines, and antisense oligodeoxynucleotides directed exclusively to the alpha1C isoform of the L-type Ca channel. Ca2+ transients and RVD in cells grown on untreated glass cover slips were inhibited by similar maneuvers, but only by antisense oligodeoxynucleotides directed to the alpha1S isoform of the L-type Ca channel. This represents the first molecular identification of the Ca channels that transduce the initiation signal for RVD by osteoblastic cells.
Kizer
N
N
Renal Division, Barnes-Jewish Hospital at the Washington University Medical Center, St. Louis, MO 63110, USA.
Harter
L
L
Hruska
K
K
Alvarez
U
U
Duncan
R
R
D000818:Animals; D001859:Bone Neoplasms / Q000378:metabolism* / Q000473:pathology; D002118:Calcium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology; D015220:Calcium Channels / Q000378:metabolism*; D020746:Calcium Channels, L-Type; D048429:Cell Size / Q000187:drug effects / Q000502:physiology; D004095:Dihydropyridines / Q000494:pharmacology; D007038:Hypotonic Solutions / Q000494:pharmacology; D009543:Nifedipine / Q000494:pharmacology; D016376:Oligonucleotides, Antisense / Q000378:metabolism; D009994:Osmolar Concentration; D010006:Osteoblasts / Q000378:metabolism / Q000473:pathology; D012516:Osteosarcoma / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D020033:Protein Isoforms; D051381:Rats; D014407:Tumor Cells, Cultured
D002121:Calcium Channel Blockers; D015220:Calcium Channels; D020746:Calcium Channels, L-Type; D004095:Dihydropyridines; D007038:Hypotonic Solutions; D016376:Oligonucleotides, Antisense; D020033:Protein Isoforms; C038806:1,4-dihydropyridine; D009543:Nifedipine; D002118:Calcium