Structural determinants of fast inactivation of high voltage-activated Ca2+ channels

The fast inactivation of voltage-dependent Ca2+ channels is a key mechanism that contributes to the precise control of Ca2+ entry into excitable cells . Recent advances have revealed that multiple structural elements contribut e to the intrinsic inactivation properties of the alpha (1) subunit, includ ing its cytoplasmic and transmembrane regions. Another major determinant of Ca2+ channel inactivation is the association with one of four types of anc illary beta subunits that differentially modulate the intrinsic inactivatio n properties of the alpha (1) subunit. This could occur partly via interact ions with the hi-terminal region of the alpha (1) subunit and through lipid modification of the a subunit. However, the latest findings suggest a mech anism in which fast Ca2+ channel inactivation could occur through physical occlusion of the pore of the channel in a manner reminiscent of Na+ and Kchannel inactivation.