title: Properties of Ba2+ currents arising from human alpha1E and alpha1Ebeta3 constructs expressed in HEK293 cells: physiology, pharmacology, and comparison to native T-type Ba2+ currents.
abstract: Currents arising from human alpha1E and alpha1Ebeta3 Ca2+ channel subunits expressed in HEK-293 cells were examined with whole-cell recording methods and compared to properties of T-current in DRG neurons studied under identical ionic conditions. Coexpression of alpha1E subunit with the beta3 subunit shifted activation to more negative potentials. Activation and deactivation of both variants were comparable at most voltages, with deactivation becoming faster, but less voltage-dependent, at more negative potentials. The inactivation time course for alpha1E and alpha1Ebeta3 currents was best described by at least two exponential components. Recovery from inactivation was markedly voltage-dependent and similar for both constructs. In comparison to alpha1E and alpha1Ebeta3 constructs, T current activation was shifted to more negative potentials, activation was typically slower, deactivation exhibited a steeper voltage-dependence, and recovery from inactivation was less voltage-dependent. Over most of the activation range, native T current inactivated more completely and in a single exponential fashion. Despite some pharmacological similarities (e.g. octanol, barbiturates) between alpha1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish alpha1E current from T-type currents. The results define several distinguishing features of alpha1E currents that distinguish them from native T-type currents.
authors.affiliation: Department of Anesthesiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Y M
authors.initials: YM
authors.lastname: Nakashima
authors.forename: S M
authors.initials: SM
authors.lastname: Todorovic
authors.forename: A
authors.initials: A
authors.lastname: Pereverzev
authors.forename: J
authors.initials: J
authors.lastname: Hescheler
authors.forename: T
authors.initials: T
authors.lastname: Schneider
authors.forename: C J
authors.initials: CJ
authors.lastname: Lingle
mesh_terms: D000584:Amiloride / Q000494:pharmacology; D001464:Barium / Q000502:physiology*; D015220:Calcium Channels / Q000737:chemistry / Q000502:physiology*; D002460:Cell Line; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D007473:Ion Channels / Q000187:drug effects / Q000502:physiology*; D009474:Neurons / Q000502:physiology; D018408:Patch-Clamp Techniques; D010446:Peptide Fragments / Q000502:physiology*; D010672:Phenytoin / Q000494:pharmacology
chemical_list: D015220:Calcium Channels; D007473:Ion Channels; D010446:Peptide Fragments; D001464:Barium; D010672:Phenytoin; D000584:Amiloride