Ca2+ store dynamics determines the pattern of activation of the store‐operated Ca2+ current ICRAC in response to InsP3 in rat basophilic leukaemia cells (original) (raw)

2000, The Journal of Physiology

In a variety of cell types, stimulation of cell-surface receptors that engage the phosphoinositide pathway evokes a biphasic increase in intracellular Ca¥: an initial inositol 1,4,5-trisphosphate (InsP×)-mediated Ca¥ release phase is followed by a smaller but sustained Ca¥ influx component (Berridge, 1993; Parekh & Penner, 1997). In most nonexcitable cells, emptying of the intracellular Ca¥ stores activates a selective Ca¥ current called ICRAC (Ca¥ releaseactivated Ca¥ current; Hoth & Penner, 1992; Parekh & Penner, 1997). Ca¥ entry through CRAC channels is necessary for prolonging the Ca¥ signal following transient Ca¥ release, for refilling the stores as well as for a host of key cellular functions including exocytosis, gene transcription and cell proliferation (Parekh & Penner, 1997). The relationship between the intracellular InsP× concentration and activation of the store-operated Ca¥ influx can be graded (Jacob, 1990) or supra-linear (Parekh et al. 1997; Hartmann & Verkhratsky, 1998; Liu et al. 1998) in different non-excitable cells. In rat basophilic leukaemia (RBL-1) cells, a model system for studying ICRAC, the amplitude of the current is steeply related to InsP× concentration with a Hill coefficient of 12 (Parekh et al. 1997). This highly non-linear behaviour probably reflects metabolism of InsP× because the non-metabolisable InsP× analogue Ins2,4,5P× generates a graded response (Hill coefficient of 1). Stimulation of cell-surface receptors that engage the phosphoinositide pathway also generates ICRAC in a non-linear manner, suggesting that this highly supra