TY - JOUR
T1 - Properties of Ba2+ currents arising from human α1E and α1Eβ3 constructs expressed in HEK293 cells
T2 - physiology, pharmacology, and comparison to native T-type Ba2+ currents
AU - Nakashima, Yasunori M.
AU - Todorovic, Slobodan M.
AU - Pereverzev, Alexei
AU - Hescheler, Juergen
AU - Schneider, Toni
AU - Lingle, Christopher J.
N1 - Funding Information:
We are grateful to Professor Dr V. Flockerzi (Homburg) for the expression vector containing the human β3 cDNA ( Murakami et al., 1996 ) and to Dr A. Ludwig and Professor F. Hofmann (München) for the anti-β3 serum. The work was financially supported by Deutsche Forschungsgemeinschaft (to AP and TS), by the NIH (GM-47969 to CL), and the Zentrum für Molekularbiologische Medizin Köln (Bundesministerium für Bildung, Wissenschaft, Forschung und Technologie, Förderkennzeichen 01 KS 9502 to TS [the author is responsible for the content of the publication]). We thank Vani Kalyanaraman for technical assistance and Dr Ed Perez-Reyes for comments on the manuscript.
PY - 1998/8
Y1 - 1998/8
N2 - Currents arising from human α1E and α1Eβ3 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 α1E subunit with the β3 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 α1E and α1Eβ3 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 α1E and α1Eβ3 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 α1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish α1E current from T-type currents. The results define several distinguishing features of α1E currents that distinguish them from native T-type currents. Copyright (C) 1998 Elsevier Science Ltd.
AB - Currents arising from human α1E and α1Eβ3 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 α1E subunit with the β3 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 α1E and α1Eβ3 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 α1E and α1Eβ3 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 α1E and T-type currents, aspects of blockade by amiloride and phenytoin appear to distinguish α1E current from T-type currents. The results define several distinguishing features of α1E currents that distinguish them from native T-type currents. Copyright (C) 1998 Elsevier Science Ltd.
KW - Ca channel subunit
KW - Ca currents
KW - Ca currents (R-type)
KW - Ca currents (T-type)
KW - LVA current
KW - α1E
UR - https://www.scopus.com/pages/publications/0031593408
U2 - 10.1016/S0028-3908(98)00097-5
DO - 10.1016/S0028-3908(98)00097-5
M3 - Article
C2 - 9833625
AN - SCOPUS:0031593408
SN - 0028-3908
VL - 37
SP - 957
EP - 972
JO - Neuropharmacology
JF - Neuropharmacology
IS - 8
ER -