CRAC activity at low agonist concentrations?

15 June 2004

Trevor Shuttleworth

Reinhold – I have a question.

I looked again at the paper you mentioned by Hermosura et al. and saw that you recorded a Ca2+ influx at very low CCh concentrations in RBL cells using fura-2 fluorescence (even when in whole-cell mode), but I could not see anything about current recordings.

Did I miss something?

If I read your posting of June 7 correctly, I understand that you believe that this entry is likely to be via CRAC (as Mike Berridge later restated). However, without specific identification of the responsible conductance as CRAC, I would question this assumption.

This may seem trivial, but I don't think it is. As statements get repeated in the literature, there seems to be an inevitable tendency to increase their impact or specificity such that a general measurement of Ca2+ entry, or even a poorly characterized current, becomes "morphed" into a specific assignment to a particular channel.

To be specific, I am not aware of any published evidence showing that CRAC channels are activated at very low agonist concentrations.

ARC channels, on the other hand, are activated by agonist concentrations at which we are just able to see the very weakest of Ca2+ signals, and continue to provide the predominant source of Ca2+ entry until sustained, elevated Ca2+ signals are seen (JBC 276: 35676-35683).