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Neuroscience. 2006 Dec;143(3):717-28. Epub 2006 Sep 22.

Determinants of the differential gating properties of Cav3.1 and Cav3.3 T-type channels: a role of domain IV?

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1
Hotchkiss Brain Institute and Department of Physiology and Biophysics, University of Calgary, 3330 Hospital Drive Northwest, Calgary, Canada T2N 4N1.

Abstract

We have investigated the channel structural determinants that underlie the difference in gating properties of Cav3.1 and Cav3.3 T-type channels, by creating a series of chimeric channel constructs in which the major transmembrane domains were swapped. The chimeras were then expressed in tsA-201 cells and subjected to whole cell patch clamp analysis. Our data reveal that domains I and IV are major determinants of the half-activation potential. Substitution of domain IV was the most important determinant of activation time constant and time constant for recovery from inactivation, with domains I and II mediating a smaller role. In contrast, the carboxy terminal region did not appear to be involved. Determinants of the time constant for inactivation could not be localized to a specific transmembrane domain, but the concomitant substitution of domains I+IV was able to partially confer the inactivation kinetics among the two wild type channels. Our data indicate that the domain IV region mediates an important role in T-type channel activation, whereas multiple channel structural determinants appear to control T-type channel inactivation.

[Indexed for MEDLINE]

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