Time-dependent regulation of capacitative Ca2+ entry by IGF-1 in human embryonic kidney cells.
In a wide variety of cells, mitogenic factors release Ca(2+) from intracellular stores. The fall of the [Ca(2+)] within the lumen of the Ca(2+)-storing organelles triggers in many cells capacitative Ca(2+) entry (CCE). The present study was performed to elucidate the effect of insulin-like growth factor (IGF-1) on CCE in human embryonic kidney (HEK 293) cells. After depletion of Ca(2+) stores by thapsigargin, CCE was assessed by the increase in cytosolic free [Ca(2+)] (Fura-2 fluorescence imaging) when raising extracellular [Ca(2+)] from 0 to physiological concentrations. IGF-1 exposure (50 ng/ml) for 4 h in serum-free medium markedly enhanced CCE, while a 24-h exposure to IGF-1 depressed CCE profoundly. As some Ca(2+) channels are highly sensitive to the cell membrane potential, and as IGF-1 has been reported to enhance K(+) channel activity, the influence of K(+) channel blockers on the IGF-1-dependent stimulation of CCE was also tested. TEA, charybdotoxin and margatoxin decreased CCE. Similar to the total capacitative calcium entry, the fraction of CCE that was sensitive to K(+) channel blockers was increased after 4 h and decreased after 24 h exposure to IGF-1. Taken together, these data suggest that IGF-1 induces a transient increase followed by a decrease of CCE, and that these effects are at least partly dependent on IGF-1-induced K(+) channel activity.
Tanneur
V
V
Department of Physiology I, University of Tuebingen, Gmelinstrasse 5, 72076 Tuebingen, Germany.
Ilgaz
D
D
Duranton
C
C
Fillon
S
S
Gamper
N
N
Huber
S M
SM
Lang
F
F
D001790:Blood Physiological Phenomena; D002118:Calcium / Q000378:metabolism*; D002460:Cell Line; D004622:Embryo, Mammalian / Q000166:cytology / Q000378:metabolism; D006801:Humans; D007334:Insulin-Like Growth Factor I / Q000502:physiology*; D007668:Kidney / Q000196:embryology*; D018408:Patch-Clamp Techniques; D026902:Potassium Channel Blockers / Q000494:pharmacology; D013997:Time Factors
D026902:Potassium Channel Blockers; D007334:Insulin-Like Growth Factor I; D002118:Calcium