Multiple structural elements contribute to the slow kinetics of the Ca v3.3 T-type channel

Abstract

Molecular cloning and expression studies established the existence of three T-type Ca2+ channel (Cav3) α1 subunits: Cav3.1 (α1G), Cav3.2 (α1H), and Cav3.3 (α1I). Although all three channels are low voltage-activated, they display considerable differences in their kinetics, with Cav3.1 and Cav3.2 channels activating and inactivating much faster than Cav3.3 channels. The goal of the present study was to determine the structural elements that confer the distinctively slow kinetics of Cav3.3 channels. To address this question, a series of chimeric channels between Cav3.1 and Cav3.3 channels were constructed and expressed in Xenopus oocytes. Kinetic analysis showed that the slow activation and inactivation kinetics of the Cav3.3 channel were not completely abolished by substitution with any one portion of the Cav3.1 channel. Likewise, the Cav3.1 channel failed to acquire the slow kinetics by simply adopting one portion of the Cav3.3 channel. These findings suggest that multiple structural elements contribute to the slow kinetics of Cav3.3 channels.