E-Conference: Defining Calcium Entry Signals
Gating of calcium entry channels
16 June 2004
These are important questions, without easy answers. Since we do not as yet have any one gating mechanism that is proven and well characterized, we do not have criteria for evaluating one or another mechanism in any given cell type.
There is certainly considerable circumstantial evidence for each of the two general mechanisms: diffusible signal, and conformational coupling. In fact, I have often stated that by selective choice of literature references, a rather solid case can be made for either one.
It is possible that this reflects different mechanisms in different cell types, or for different channel types. A case in point is the mechanism of interaction between plasma membrane Ca2+ channels and intracellular ryanodine release channels in two cell types, skeletal muscle and cardiac muscle. In one case the interaction is clearly a direct one, in the other, clearly the interaction involves a diffusible signal, in this case Ca2+ itself.
As to what the criteria are for demonstrating that something is part of the gating mechanism, I think these are not different from those already discussed for identifying the channels. One would like to identify or speculate on candidates by whatever basis, and investigate their involvement by a combination of positive (add it, see if it works) and negative (knock it out, or inhibit it) approaches. There has been some encouraging work along these lines for the case of the CIF - PLA2 (calcium inlux factor- phospholipase A2) hypothesis, already discussed in this forum.
A final criterion I would invoke for both the gating mechanism question and the channel question is that we need to eventually achieve a consensus of experimental observations and interpretation among a number of different laboratories.