Role of Repeat I in the fast inactivation kinetics of the CaV2.3 channel

被引:12
作者
Bernatchez, G [1 ]
Berrou, L [1 ]
Benakezouh, Z [1 ]
Ducay, J [1 ]
Parent, L [1 ]
机构
[1] Univ Montreal, Dept Physiol, Membrane Transport Res Grp, Downtown Stn, Montreal, PQ H3C 3J7, Canada
来源
BIOCHIMICA ET BIOPHYSICA ACTA-BIOMEMBRANES | 2001年 / 1514卷 / 02期
基金
英国医学研究理事会;
关键词
Xenopus oocyte; structure-function; site directed mutagenesis; electrophysiology; voltage-dependent Ca2+ channel; beta subunit;
D O I
10.1016/S0005-2736(01)00373-X
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The molecular basis for inactivation in Ca(V)2.3 (alpha 1E) channels was studied after expression of alpha 1E/alpha 1C (Ca(V)2.3/Ca(V)1.2) chimeras in Xenopus oocytes. In the presence of 10 mM Ba2+, the CEEE chimera (Repeat I+part of the I-II linker from Ca(V)1.2) displayed inactivation properties similar to Ca(V)1.2 despite being more than 90% homologous to Ca(V)2.3. The transmembrane segments of Repeat I did not appear to be crucial as inactivation of EC(ISI-6)EEE was not significantly different than Ca(V)2.3. In contrast, EC(AID)EEE, with the P-subunit binding domain from Ca(V)1.2, tended to behave like Ca(V)1.2 in terms of inactivation kinetics and voltage dependence. A detailed kinetic analysis revealed nonetheless that CEEE and EC(AID)EEE retained the fast inactivation time constant (tau (fast) approximate to 20-30 ms) that is a distinctive feature of Ca(V)2.3. Altogether, these data suggest that the region surrounding the AID binding site plays a pivotal albeit not exclusive role in determining the inactivation properties of Ca(V)2.3. (C) 2001 Elsevier Science B.V. All rights reserved.
引用
收藏
页码:217 / 229
页数:13
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