title: K(V)alpha1 channels in murine arterioles: differential cellular expression and regulation of diameter.
abstract: The primary objectives of this study were to reveal cell-specific expression patterns and functions of voltage-gated K(+) channel (K(V)alpha1) subunits in precapillary arterioles of the murine cerebral circulation. K(V)alpha1 were detected using peptide-specific antibodies in immunofluorescence and Western blotting assays. K(V)1.2 was localized almost exclusively to endothelial cells, whereas K(V)1.5 was discretely localized to the nerves and nerve terminals that innervate the arterioles. K(V)1.5 also localized specifically to arteriolar nerves in human pial membrane. K(V)1.5 was notable for its absence from smooth muscle cells. K(V)1.3, K(V)1.4, and K(V)1.6 were localized to endothelial and smooth muscle cells, although K(V)1.4 had a low expression level. K(V)1.1 was not expressed. Therefore, we show that different cell types of pial arterioles have distinct physiological expression profiles of K(V)alpha1, conferring the possibility of differential modulation by extracellular and second messengers. Furthermore, we show recombinant agitoxin-2 and margatoxin are potent vasoconstrictors, suggesting that K(V)alpha1 subunits have a major function in determining arteriolar resistance to blood flow.
authors.affiliation: School of Biomedical Sciences, University of Leeds, Leeds LS2 9JT, United Kingdom.
authors.forename: A
authors.initials: A
authors.lastname: Cheong
authors.forename: A M
authors.initials: AM
authors.lastname: Dedman
authors.forename: S Z
authors.initials: SZ
authors.lastname: Xu
authors.forename: D J
authors.initials: DJ
authors.lastname: Beech
mesh_terms: D000818:Animals; D001160:Arterioles / Q000378:metabolism*; D015153:Blotting, Western; D002540:Cerebral Cortex / Q000098:blood supply / Q000378:metabolism; D003435:Crotalid Venoms / Q000494:pharmacology; D051668:Delayed Rectifier Potassium Channels; D066298:In Vitro Techniques; D051662:Kv1.1 Potassium Channel; D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009498:Neurotoxins / Q000494:pharmacology; D009928:Organ Specificity; D010841:Pia Mater / Q000098:blood supply / Q000378:metabolism; D015221:Potassium Channels / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D012604:Scorpion Venoms; D017386:Sequence Homology, Amino Acid; D014654:Vascular Patency / Q000187:drug effects / Q000502:physiology*
chemical_list: D003435:Crotalid Venoms; D051668:Delayed Rectifier Potassium Channels; C496947:Kcna1 protein, mouse; C496970:Kcna2 protein, mouse; C496974:Kcna3 protein, mouse; C496978:Kcna4 protein, mouse; C496982:Kcna5 protein, mouse; D051663:Kv1.2 Potassium Channel; D051664:Kv1.3 Potassium Channel; D051665:Kv1.4 Potassium Channel; D051666:Kv1.5 Potassium Channel; D009498:Neurotoxins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D012333:RNA, Messenger; D011994:Recombinant Proteins; D012604:Scorpion Venoms; D051662:Kv1.1 Potassium Channel; C077910:margatoxin; C070121:beta-agkistrodotoxin