Calcium channels: The β‐subunit increases the affinity of dihydropyridine and Ca2+ binding sites of the α1‐subunit

FEBS Letters

Glossmann, Hartmut¹  Mitterdorfer, Jörg¹  Froschmayr, Monika¹  Striessnig, Jörg¹  Grabner, Manfred¹ 

[1] Institut für Biochemische Pharmakologie, Universität Innsbruck, Peter Mayrstr. 1, A-6020 Innsbruck, Austria

关键词: Ca2+ channel;    β subunit;    cDNA expression;    Ca2+ antagonist;    Radioligand binding;    DHP;    dihydropyridine;    PCR;    polymerase chain reaction;    SDS;    sodium dodecyl sulfate;   

DOI  :  10.1016/0014-5793(94)00938-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

A Ca²⁺ channel α₁-subunit derived from rabbit heart was transiently expressed in COS-7 cells. The dihydropyridine (+)-isradipine had low affinity (K _i = 34.3 nM) for the α₁-subunit in the absence of the β-subunit due to rapid dissociation (k ₋₁ = 0.11 min⁻¹). Co-expression of the β-subunit resulted in a ⪢ 35-fold increase in (+)-isradipine binding affinity (K _i = 0.9 nM) due to decreased dissociation (k ₋₁ of 0.007 min⁻¹). Higher DHP binding affinity was associated with an increase of the apparent affinity of Ca²⁺ ions for the channel. Our data suggest that the β-subunit affects the coordination of Ca²⁺ ions with sites that are coupled to the dihydropyridine binding domain and by this mechanism increases the affinity for these ligands.

【 授权许可】

Unknown