Capacitative calcium entry.

The original idea that calcium might enter cells through a capacitative mechanism was first introduced by Jim Putney [1]. The somewhat surprising hypothesis was that calcium entry was regulated by the state of filling of the calcium stores. By analogy with a capacitor in an electrical circuit, the calcium stores prevent entry when they are charged up but immediately begin to promote entry as soon as stored calcium is discharged. This capacitative entry mechanism is present in many cells and has properties which are very similar from one cell to the next [2-6]. Capacitative calcium entry can be switched on by a great variety of stimuli such as normal agonists or pharmacological agents all of which share a common property of releasing stored calcium. Examples include calcium-mobilizing agonists [7-13], the calcium-mobilizing second messenger inositol 1,4,5trisphosphate (InsP3) [11,12,14-18], the calcium ionophore ionomycin [14,19], inhibitors of the endoplasmic reticulum (ER) pumps such as thapsigargin [8,10,12,20] and cyclopiazonic acid [20,21] or simply by incubating cells in Ca2+-free conditions [12,14,15]. All this evidence indicates that the entry of external calcium is somehow controlled by the calcium content of the ER. This review is focused primarily on the mechanism ofcapacitative Ca2+ entry.