Ca2+ channel moving tail:: link between Ca2+-induced inactivation and Ca2+-signal transduction

Ca2+-induced inactivation is an important property of L-type voltage-gated Ca2+ channels. However, the underlying mechanisms are not yet understood well. There is general agreement that calmodulin (CaM) binds, in a Ca2+-dependent manner, to C-terminal motifs LA and IQ of the pore-forming alpha1c-subunit and acts as a sensor that conveys Ca2+-induced inactivation. New data indicate that both Ca2+-induced inactivation and Ca2+ signal transduction depend on the voltage-gated mobility of the C-terminal tail of the alpha1c-subunit. It is proposed that LA is a Ca2+-sensitive lock for the mechanism of slow voltage-dependent inactivation of the channel. A Ca2+-dependent switch of CaM from LA to 10 removes CaM from the inner mouth of the pore and thus eliminates slow inactivation by facilitating the constriction of the pore. The mobile tail then shuttles the Ca2+-CaM-IQ complex to a downstream target of the Ca2+ signaling cascade, where Ca2+ is released as an activating stimulus. Apo-CaM rebinds to LA and returns to the pore for a new cycle of Ca2+ signal transduction.