Extracellular calcium-dependent regulation of transmembrane calcium fluxes in murine keratinocytes.
Because the level of extracellular Ca2+ is an important stimulus for differentiation of epidermal cells in vitro, we characterized the extracellular Ca(2+)-dependent transmembrane Ca2+ fluxes in BALB/MK mouse keratinocytes. Increasing levels of extracellular Ca2+, ranging from 0.07 to 1.87 mM, stimulated the rate of 45Ca2+ uptake into these cells 10- to 70-fold and doubled the rate of 45Ca2+ efflux. The divalent cations, Ni2+ and Co2+, were able to block the influx of Ca2+, but dihydropyridines and verapamil were not. Furthermore, 10 to 100 microM of the trivalent cation La3+ induced a dose-dependent 2- to 100-fold increase of Ca2+ uptake, independently of the level of extracellular Ca2+. These observations suggest that keratinocytes possess a cell-surface "Ca(2+)-receptor," activation of which stimulates the influx of 45Ca2+ through a type of voltage-independent, receptor-operated Ca2+ channels. Epidermal growth factor induced an accumulation of 45Ca2+ of a much smaller magnitude than elevations of the level of extracellular Ca2+, without a detectable increase of Ca2+ efflux. Thus, the divergent cellular responses of keratinocytes to EGF and extracellular Ca2+ may be due, in part, to the distinct changes in transmembrane Ca2+ fluxes that these two stimuli generate. Treatment of cells with type beta transforming growth factor led to a gradual 6-fold increase of the Ca(2+)-activated rate of Ca2+ uptake over a period of 4 hours, but reduced the Ca2+ efflux by approximately 50% within 10 minutes. Thus, type beta transforming growth factor apparently stimulates Ca2+ influx indirectly, but may control the differentiation of keratinocytes by direct inhibition of Ca2+ efflux pumps.
Reiss
M
M
Department of Medicine, Yale University School of Medicine, New Haven, Connecticut 06510.
Lipsey
L R
LR
Zhou
Z L
ZL
D000818:Animals; D002118:Calcium / Q000378:metabolism*; D015220:Calcium Channels / Q000378:metabolism; D002460:Cell Line; D003035:Cobalt / Q000494:pharmacology; D015603:Keratinocytes / Q000378:metabolism*; D007811:Lanthanum / Q000494:pharmacology; D051379:Mice; D009532:Nickel / Q000494:pharmacology; D009553:Nimodipine / Q000494:pharmacology; D009568:Nitrendipine / Q000494:pharmacology; D014700:Verapamil / Q000494:pharmacology
D015220:Calcium Channels; D003035:Cobalt; D009553:Nimodipine; D007811:Lanthanum; D009532:Nickel; D009568:Nitrendipine; D014700:Verapamil; D002118:Calcium