Molecular correlates of the M-current in cultured rat hippocampal neurons

被引:170
作者
Shah, MM [1 ]
Mistry, M [1 ]
Marsh, SJ [1 ]
Brown, DA [1 ]
Delmas, P [1 ]
机构
[1] UCL, Dept Pharmacol, Wellcome Lab Mol Pharmacol, London WC1E 68T, England
来源
JOURNAL OF PHYSIOLOGY-LONDON | 2002年 / 544卷 / 01期
基金
英国惠康基金;
关键词
D O I
10.1113/jphysiol.2002.028571
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
M-type K+ currents (I-K(M)) play a key role in regulating neuronal excitability. In sympathetic neurons, M-channels are thought to be composed of a heteromeric assembly of KCNQ2 and KCNQ3 K+ channel subunits. Here, we have tried to identify the KCNQ subunits that are involved in the generation of I-K(M) in hippocampal pyramidal neurons cultured from 5- to 7-day-old rats. RT-PCR of either CA1 or CA3 regions revealed the presence of KCNQ2, KCNQ3, KCNQ4 and KCNQ5 subunits. Single-cell PCR of dissociated hippocampal pyramidal neurons gave detectable signals for only KCNQ2, KCNQ3 and KCNQ5; where tested, most also expressed mRNA for the vesicular glutamate transporter VGLUT1. Staining for KCNQ2 and KCNQ5 protein showed punctate fluorescence on both the somata and dendrites of hippocampal neurons. Staining for KCNQ3 was diffusely distributed whereas KCNQ4 was undetectable. In perforated patch recordings, linopirdine, a specific M-channel blocker, fully inhibited I-K(M) with an IC50 of 3.6 +/- 1.5 muM. In 70 % of these cells, TEA fully suppressed I-K(M) with an IC50 of 0.7 +/- 0.1 mm. In the remaining cells, TEA maximally reduced I-K(M) by only 59.7 +/- 5.2 % with an IC50 of 1.4 +/- 0.3 mm; residual I-K(M) was abolished by linopirdine. Our data suggest that KCNQ2, KCNQ3 and KCNQ5 subunits contribute to I-K(M) in these neurons and that the variations in TEA sensitivity may reflect differential expression of KCNQ2, KCNQ3 and KCNQ5 subunits.
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收藏
页码:29 / 37
页数:9
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