The role of intracellular Ca2+ release channels:

4 June 2004

Victoria M. Bolotina

Do InsP3 receptors or RyR, or both, mediate or modify Ca2+ entry events?

Either of these two receptors may affect Ca2+ entry, but they do not seem to be required and/or sufficient for activation of store-operated calcium entry (SOC). From all the data accumulated so far, it looks like whatever you do with InsP3 receptors or Ryanodine receptors (RyR), you still need a stimulus (depletion of the stores) to activate SOC and Ca2+ influx. So, intracellular Ca2+ release channels may modulate (shape) capicitative calcium entry (CCE) response (still to be determined how), but they do not seem to trigger it.

If one will look at different schemes in the papers devoted to the direct coupling model -- it is amazing how this model has evolved from a simple "physical link of InsP3R with SOC" into increasingly complicated and rather confusing arrangements that are now needed to tighten the growing number of loose ends.

So, does such complexity mean that physical coupling does not exist? Not at all! It can certainly exist, but most probably not in a way how it is presently viewed. One of theoretical possibilities is that conformational coupling may play a totally different role in the store-operated pathway -- for example, it may be not a trigger, but a "positioning", or some other kind of tuning or accessory device. This is, of course, pure speculation at this point, which should be viewed as a simple invitation for re-interpretation of many valuable pieces of experimental data from some totally different point of view, which may result in a new break through in this intriguing direction.