Mechanism of Ca2+ -dependent desensitization in TRP channels

The 30+ members of the family of TRP channels are diverse in their physiological roles, yet the mechanisms that regulate their gating may be conserved. In particular, all TRP channels show an activity-dependent inhibition which is mediated by Ca2+. The mechanism by which Ca2+ inhibits TRP channels is currently a matter of intense debate, with Ca2+ -regulated kinases, phosphatases, phospholipases and calmodulin all proposed to be involved. In this review, we will discuss different mechanisms for Ca2+ -dependent desensitization in TRP channels. We will conclude with a model that focuses on Ca2+ -dependent activation of phospholipase C and Ca2+ binding to calmodulin and propose that the phospholipase C and calmodulin pathways are structurally and functionally coupled.