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Pflügers Archiv

, Volume 433, Issue 4, pp 523–532 | Cite as

Functional expression of rat brain cloned α1E calcium channels in COS-7 cells

  • G. J. Stephens
  • Karen M. Page
  • J. Russell Burley
  • Nicholas S. Berrow
  • Annette C. Dolphin
ORIGINAL ARTICLE

Abstract

 The properties of the rat brain α1E Ca2+ channel subunit and its modulation by accessory rat brain α2-δ and β1b subunits were studied by transient transfection in a mammalian cell line in order to attempt to reconcile the debate as to whether α1E forms a low-voltage-activated (LVA) or high-voltage-activated (HVA) Ca2+ channel and to examine its pharmacology in detail. α1E alone was capable of forming an ion-conducting pore in COS-7 cells. The properties of heteromultimeric α1E/α2-δ/β1b channels were largely dictated by the presence of the β1b subunit, which increased current density and tended to produce a hyperpolarizing shift in the voltage dependence of activation and inactivation. α1E/α2-δ/β1b channels did not appear to be regulated by Ca2+-induced inactivation. α1E was shown to exhibit a unique pharmacological profile. ω-Agatoxin IVA blocked the current in a dose-dependent manner with an IC50 of approximately 50 nM and a maximum inhibition of about 80%, whilst ω-conotoxin MVIIC was without effect. The 1,4-dihydropyridine (DHP) antagonist nicardipine (1 μM) produced an inhibition of 51 ± 7%, whereas the DHP agonist S-(–)BAY K 8644 was without effect. Our findings suggest a re-evaluation of the classification of the α1E Ca2+ channel subunit; we propose that rat brain α1E forms a novel Ca2+ channel with properties more similar to a subtype of LVA than HVA Ca2+ current.

Key words Cloned Ca2+ channel subunits ω-Agatoxin IVA Nicardipine 

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Copyright information

© Springer-Verlag Berlin Heidelberg 1997

Authors and Affiliations

  • G. J. Stephens
    • 1
  • Karen M. Page
    • 1
  • J. Russell Burley
    • 1
  • Nicholas S. Berrow
    • 1
  • Annette C. Dolphin
    • 1
  1. 1.Department of Pharmacology, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UKGB

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