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Endothelial SK(Ca) and IK(Ca) channels regulate brain parenchymal arteriolar diameter and cortical cerebral blood flow.

Hannah, Rachael M; Dunn, Kathryn M; Bonev, Adrian D; Nelson, Mark T

Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism. 2011;31(5):1175-1186.

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Abstract

Calcium-sensitive potassium (K(Ca)) channels have been shown to modulate the diameter of cerebral pial arteries; however, little is known regarding their roles in controlling cerebral parenchymal arterioles (PAs). We explored the function and cellular distribution of small-conductance (SK(Ca)) and intermediate-conductance (IK(Ca)) K(Ca) channels and large-conductance K(Ca) (BK(Ca)) channels in endothelial cells (ECs) and smooth muscle cells (SMCs) of PAs. Both SK(Ca) and IK(Ca) channels conducted the outward current in isolated PA ECs (current densities, ~20 pA/pF and ~28 pA/pF at +40 mV, respectively), but these currents were not detected in PA SMCs. In contrast, BK(Ca) currents were prominent in PA SMCs (~154 pA/pF), but were undetectable in PA ECs. Pressurized PAs constricted to inhibition of SK(Ca) (~16%) and IK(Ca) (~16%) channels, but were only modestly affected by inhibition of BK(Ca) channels (~5%). Blockade of SK(Ca) and IK(Ca) channels decreased resting cortical cerebral blood flow (CBF) by ~15%. NS309 (6,7-dichloro-1H-indole-2,3-dione3-oxime), a SK(Ca)/IK(Ca) channel opener, hyperpolarized PA SMCs by ~27 mV, maximally dilated pressurized PAs, and increased CBF by ~40%. In conclusion, these data show that SK(Ca) and IK(Ca) channels in ECs profoundly modulate PA tone and CBF, whereas BK(Ca) channels in SMCs only modestly influence PA diameter.

Bibliographic metadata

Type of resource:
Content type:
Publication status:
Accepted
Publication type:
Published date:
Language:
eng
Abbreviated journal title:
ISSN:
Place of publication:
United States
Volume:
31
Issue:
5
Start page:
1175
End page:
1186
Total:
11
Pagination:
1175-1186
Digital Object Identifier:
10.1038/jcbfm.2010.214
Pubmed Identifier:
21179072
Pii Identifier:
jcbfm2010214
Attached files embargo period:
Immediate release
Attached files release date:
2nd October, 2014
Access state:
Active

Institutional metadata

University researcher(s):

Record metadata

Manchester eScholar ID:
uk-ac-man-scw:201860
Created by:
Nelson, Mark
Created:
19th July, 2013, 13:40:17
Last modified by:
Nelson, Mark
Last modified:
2nd October, 2014, 18:57:55

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