Functional expression of rat brain cloned α1E calcium channels in COS-7 cells |
| |
Authors: | G J Stephens Karen M Page J Russell Burley Nicholas S Berrow Annette C Dolphin |
| |
Institution: | (1) Department of Pharmacology, Royal Free Hospital School of Medicine, Rowland Hill Street, London NW3 2PF, UK, GB |
| |
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.
Received: 30 August 1996 / Received after revision and accepted: 28 October 1996 |
| |
Keywords: | Cloned Ca2+ channel subunits ω -Agatoxin IVA Nicardipine |
本文献已被 SpringerLink 等数据库收录! |
|