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Effect of small and intermediate conductance calcium activated potassium channel modulation on cortical cerebral blood flow in vivo
Author(s) -
Dunn Kathryn M.,
Nelson Mark T.
Publication year - 2009
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.23.1_supplement.613.24
Subject(s) - apamin , chemistry , cerebral blood flow , in vivo , endocrinology , medicine , calcium activated potassium channel , calcium , potassium channel , nitric oxide , sk channel , biophysics , biochemistry , biology , ion channel , receptor , microbiology and biotechnology , organic chemistry
Pharmacological studies using selective inhibitors and activators of small and intermediate conductance calcium‐activated potassium channels (SK Ca and IK Ca ) indicate that these channels participate in endothelium‐derived hyperpolarization responses and modulate vascular tone in isolated cerebral arteries. However, the relevance of SK Ca and IK Ca channel activity in the regulation of cerebral blood flow (CBF) in vivo has not been determined. The present study investigated the effect of SK Ca and IK Ca modulation on cortical CBF in vivo using laser Doppler flowmetry. Superfusion of inhibitors of SK Ca and IK Ca (apamin, 300 nM, and TRAM‐34, 10 μM, respectively) through a cranial window over the somatosensory cortex in mouse reduced resting cortical CBF by 17 ± 4 % (n=6, p<0.001). This was similar to the reduction in resting CBF with administration of the nonselective nitric oxide synthase inhibitor, N ? ‐nitro‐L‐arginine (L‐NNA, 1 mM), of 14 ± 6 % (n=6, p<0.01). Superfusion of the SK Ca and IK Ca activator, NS309, produced a rapid and robust increase in cortical CBF of 37 ± 9 %, which was largely blocked by apamin and TRAM‐34 (n=7, p<0.01). Inhibition of nitric oxide synthesis with L‐NNA had no effect on the increase in CBF in response to NS309. These results indicate that SK Ca and IK Ca channels are involved in the regulation of cortical CBF in vivo under resting conditions. The results suggest that SK Ca and IK Ca channels may also mediate in vivo cerebral vascular responses to metabolic and humoral stimuli, and may be potential therapeutic targets for maintenance of cerebral perfusion. This study was supported by National Heart, Lung, and Blood Institute grant HL‐44455 .