title: Expression and alteration of BKCachannels in the sphincter of Oddi's from rabbits with hypercholesterolemia.
abstract: This study aimed to investigate the expression and function of BKCachannels in the Sphincter of Oddi (SO) in a rabbit model of hypercholesterolemia (HC). New Zealand white rabbits were randomly divided into 2 groups: the control group was fed standard chow (n = 18) whereas the high-cholesterol group was fed cholesterol-enriched chow containing 1.5% cholesterol (n = 18). The serum cholesterol level was significantly greater in the HC groups than in the control group, but there was no significant difference in body weight between the control and HC groups. Although the total protein expression of BKCaα- and β1-subunit was not significantly different between the control and HC groups, the Tyr-phosphorylation of BKCaα-subunit was significantly decreased in the HC group than in the control group. In addition, hypercholesterolemia significantly increased Acetylcholine (ACh)-induced contraction of the SO rings. Pretreatment with 30 μM NS1619, a BKCachannel agonist, significantly reduced ACh-induced contraction of the SO rings in HC rabbits. Moreover, pretreatment with 100 μM Na3OV4, a protein tyrosine phosphatase inhibitor, significantly reduced ACh-induced contraction of the SO rings in HC rabbits, whereas it significantly increased upon pretreating with 10 μM Genistein, a tyrosine kinase inhibitor. Whole-cell patch clamp recordings showed that BKCacurrent density was significantly lower in SOSMCs from HC group than that from control group. Our findings suggest that hypercholesterolemia-induced downregulation of BKCachannel, and Tyr-phosphorylation of BKCaα-subunit may contribute to the hyperresponsiveness of the SO ring in HC rabbits.
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Dan
authors.identifier: http://orcid.org/0000-0001-8376-4396
authors.initials: D
authors.lastname: Feng
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Haiyan
authors.identifier: http://orcid.org/0000-0001-6327-2976
authors.initials: H
authors.lastname: Nan
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Wen
authors.identifier: http://orcid.org/0000-0001-6473-4888
authors.initials: W
authors.lastname: Wang
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Linfeng
authors.identifier: http://orcid.org/0000-0001-8824-6117
authors.initials: L
authors.lastname: Yan
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Pang
authors.identifier: http://orcid.org/0000-0002-2012-8111
authors.initials: P
authors.lastname: Du
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Lin
authors.identifier: http://orcid.org/0000-0001-5399-3825
authors.initials: L
authors.lastname: Zuo
authors.affiliation: b Department of Pharmacology, School of Pharmacy , Fourth Military Medical University , Xi'an , China.
authors.forename: Kun
authors.identifier: http://orcid.org/0000-0003-3852-6852
authors.initials: K
authors.lastname: Zhang
authors.affiliation: b Department of Pharmacology, School of Pharmacy , Fourth Military Medical University , Xi'an , China.
authors.forename: Minggao
authors.identifier: http://orcid.org/0000-0002-7539-3887
authors.initials: M
authors.lastname: Zhao
authors.affiliation: a Department of Radiology , Tangdu Hospital, Fourth Military Medical University , Xi'an , China.
authors.forename: Guangbin
authors.identifier: http://orcid.org/0000-0002-7935-9803
authors.initials: G
authors.lastname: Cui
mesh_terms: D000818:Animals; D002784:Cholesterol / Q000097:blood; D002791:Cholesterol, Dietary / Q000494:pharmacology; D005786:Gene Expression Regulation / Q000187:drug effects; D006937:Hypercholesterolemia / Q000097:blood / Q000378:metabolism*; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits / Q000378:metabolism*; D011817:Rabbits; D009803:Sphincter of Oddi / Q000187:drug effects / Q000378:metabolism*
chemical_list: D002791:Cholesterol, Dietary; D051037:Large-Conductance Calcium-Activated Potassium Channel alpha Subunits; D002784:Cholesterol
keywords: BKCa channels; hypercholesterolemia; muscle tone; the Sphincter of Oddi; tyrosine phosphorylation