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- PMID: 21506954
- UKPMCID: 21506954
- DOI: 10.1111/j.1476-5381.2011.01447.x
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Intermediate-conductance calcium-activated potassium channels participate in neurovascular coupling.
Longden, T A; Dunn, K M; Draheim, H J; Nelson, M T; Weston, A H; Edwards, G
British journal of pharmacology. 2011;164(3):922-33.
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Full-text held externally
- PMID: 21506954
- UKPMCID: 21506954
- DOI: 10.1111/j.1476-5381.2011.01447.x
Abstract
BACKGROUND AND PURPOSE: Controlling vascular tone involves K(+) efflux through endothelial cell small- and intermediate-conductance calcium-activated potassium channels (K(Ca)2.3 and K(Ca)3.1, respectively). We investigated the expression of these channels in astrocytes and the possibility that, by a similar mechanism, they might contribute to neurovascular coupling. EXPERIMENTAL APPROACH: Transgenic mice expressing enhanced green fluorescent protein (eGFP) in astrocytes were used to assess K(Ca)2.3 and K(Ca)3.1 expression by immunohistochemistry and RT-PCR. K(Ca) currents in eGFP-positive astrocytes were determined in situ using whole-cell patch clamp electrophysiology. The contribution of K(Ca)3.1 to neurovascular coupling was investigated in pharmacological experiments using electrical field stimulation (EFS) to evoke parenchymal arteriole dilatation in FVB/NJ mouse brain slices and whisker stimulation to evoke changes in cerebral blood flow in vivo, measured by laser Doppler flowmetry. KEY RESULTS: K(Ca)3.1 immunoreactivity was restricted to astrocyte processes and endfeet and RT-PCR confirmed astrocytic K(Ca)2.3 and K(Ca)3.1 mRNA expression. With 200 nM [Ca(2+)](i) , the K(Ca)2.1-2.3/K(Ca)3.1 opener NS309 increased whole-cell currents. CyPPA, a K(Ca)2.2/K(Ca)2.3 opener, was without effect. With 1 µM [Ca(2+)](i) , the K(Ca)3.1 inhibitor TRAM-34 reduced currents whereas apamin (K(Ca)2.1-2.3 blocker) had no effect. CyPPA also inhibited currents evoked by NS309 in HEK293 cells expressing K(Ca)3.1. EFS-evoked Fluo-4 fluorescence confirmed astrocyte endfoot recruitment into neurovascular coupling. TRAM-34 inhibited EFS-evoked arteriolar dilatation by 50% whereas charybdotoxin, a blocker of K(Ca)3.1 and the large-conductance K(Ca) channel, K(Ca)1.1, inhibited dilatation by 82%. TRAM-34 reduced the cortical hyperaemic response to whisker stimulation by 40%. CONCLUSION AND IMPLICATIONS: Astrocytes express functional K(Ca)3.1 channels, and these contribute to neurovascular coupling.