Determinants of the Differential Gating Properties of Cav3.1 and Cav3.3 T-type Channels: a Role of Domain IV?
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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.
El Ghaleb Y, Flucher B Handb Exp Pharmacol. 2023; 279:263-288.
PMID: 36592228 DOI: 10.1007/164_2022_631.
Selective inhibition of neuronal Ca3.3 T-type calcium channels by TAT-based channel peptide.
Cmarko L, Weiss N Mol Brain. 2020; 13(1):95.
PMID: 32560664 PMC: 7304182. DOI: 10.1186/s13041-020-00636-y.
Jurkovicova-Tarabova B, Cmarko L, Rehak R, Zamponi G, Lacinova L, Weiss N Mol Brain. 2019; 12(1):34.
PMID: 30961646 PMC: 6454634. DOI: 10.1186/s13041-019-0457-0.
Garza-Lopez E, Lopez J, Hagen J, Sheffer R, Meiner V, Lee A J Biol Chem. 2018; 293(37):14444-14454.
PMID: 30054272 PMC: 6139563. DOI: 10.1074/jbc.RA118.003681.
Sanchez-Sandoval A, Herrera Carrillo Z, Diaz Velasquez C, Delgadillo D, Rivera H, Gomora J PLoS One. 2018; 13(2):e0193490.
PMID: 29474447 PMC: 5825144. DOI: 10.1371/journal.pone.0193490.