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

Neuroscience. 2006 Dec;143(3):717-28. doi: 10.1016/j.neuroscience.2006.08.023. Epub 2006 Sep 22.


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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Calcium Channels, T-Type / genetics
  • Calcium Channels, T-Type / physiology*
  • Cell Line, Transformed
  • Dose-Response Relationship, Radiation
  • Electric Stimulation / methods
  • Humans
  • Ion Channel Gating / physiology*
  • Ion Channel Gating / radiation effects
  • Membrane Potentials / physiology
  • Membrane Potentials / radiation effects
  • Membrane Transport Proteins / genetics
  • Membrane Transport Proteins / physiology*
  • Mutagenesis / physiology
  • Mutant Chimeric Proteins / physiology
  • Patch-Clamp Techniques / methods
  • Protein Structure, Tertiary / physiology
  • Transfection / methods


  • CACNA1G protein, human
  • CACNA1I protein, human
  • Calcium Channels, T-Type
  • Membrane Transport Proteins
  • Mutant Chimeric Proteins