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E-Conference: Defining Calcium Entry Signals

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Calcium entry at low agonist concentrations

16 June 2004

Trevor Shuttleworth

A couple of points:

1) I too am not aware of any published report showing SOC channel activity under "truly physiological" conditions. However, in contrast, we ARE able to show ARC channel activity under these conditions (i.e. at the same agonist concentrations that we are just able to see the very weakest Ca2+ signal, and in perforated patch experiments etc.).

These findings would contradict your comment that fluorescence methods are (necessarily) a much more sensitive measurement- for Ca2+ than a measurement of current - at least under these conditions. It is precisely because we CAN measure the activation of a Ca2+-selective conductance at the identical agonist concentrations at which Ca2+ signals can begin to be seen that led us to the conclusion we have been proposing for the past few years, namely that SOC channels are not active at such concentrations, but ARC channels are!

2) A minor comment re. the pharmacology. Lanthanides at 1 uM will block ARC channels (by approximately 50%), so submicromolar would be required if ARC and SOC channels are to be clearly distinguished.

I agree with the "selectivity" of 2-APB for the channels themselves, but when studying agonist-stimulated responses, our experience indicates that almost anything can happen! I think this is because such responses involve so many steps at which 2-APB can be having any number of nonspecific effects.

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