Gender-specific difference in cardiac ATP-sensitive K(+) channels.

Gender-specific difference in cardiac ATP-sensitive K(+) channels. Research Abstract Details 

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Gender-specific difference in cardiac ATP-sensitive K(+) channels. Abstract Text:

H J Ranki,G R Budas,R M Crawford,A Jovanovi?,

OBJECTIVES: The main objective of this study was to establish whether gender regulates expression and/or properties of cardiac ATP-sensitive K(+) (K(ATP)) channels. BACKGROUND: Recently, evidence has been provided that differing cardiac responses in males and females to metabolic stress may result from gender-specific difference(s) in the efficiency of endogenous cardioprotective mechanism(s) such as K(ATP) channels. METHODS: A reverse transcription polymerase chain reaction (RT-PCR) using primers specific for Kir6.2, Kir6.1 and SUR2A subunits was performed on total RNA from guinea pig ventricular tissue. Western blotting using anti-Kir6.2 and anti-SUR2A antibodies was performed on cardiac membrane fraction. Whole-cell, single-channel electrophysiology and digital epifluorescent Ca(2+) imaging were performed on isolated guinea pig ventricular cardiomyocytes. RESULTS: The RT-PCR revealed higher levels of SUR2A, but not Kir6.1 and Kir6.2, messenger RNA in female tissue relative to male tissue, while much higher levels of both Kir6.2 and SUR2A proteins in cardiac membrane fraction in female tissue compared with male tissue were found. In both male and female tissue, pinacidil (100 microM), a K(ATP) channel opener, induced outward whole-cell currents. The current density of the pinacidil-sensitive component was significantly higher in female tissue than it was in male tissue, while no differences in single K(ATP) channel properties between genders were observed. Ischemia-reperfusion challenge induced significant intracellular Ca(2+) loading in male, but not female, cardiomyocytes. To test the hypothesis that SUR2A expression is the limiting factor in K(ATP) channel formation, we took different volumes of Kir6.2 and SUR2A complementary DNA (cDNA) from the same cDNA pool and subjected them to PCR. In order to obtain a band having 50% of the maximal intensity, a volume of SUR2a cDNA approximately 20 times the volume of Kir6.2 cDNA was required. CONCLUSIONS: This study has demonstrated that female tissue expresses higher levels of functional cardiac K(ATP) channels than male tissue due to the higher expression of the SUR2A subunit, which has an impact on cardiac response to ischemia-reperfusion challenge.

Gender-specific difference in cardiac ATP-sensitive K(+) channels. Publishing Authors By Initials

HJ Ranki,GR Budas,RM Crawford,A Jovanovi?,

For similar chemical actions and uses: pharmacologic actions: therapeutic uses: cardiovascular agents: vasodilator agents research abstracts see: chemical actions and uses: pharmacologic actions: therapeutic uses: cardiovascular agents: vasodilator agents research

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Gender-specific difference in cardiac ATP-sensitive K(+) channels. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: Journal of the American College of Cardiology

VOLUME: 38

Page Numbers: 906-15

Journal Abbreviation: J. Am. Coll. Cardiol.

ISSN: 0735-1097

DAY: 17

MONTH: Sep

YEAR: 2001

Gender-specific difference in cardiac ATP-sensitive K(+) channels. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 8301365

Gender-specific difference in cardiac ATP-sensitive K(+) channels. Keywords Mesh Terms:

KEYWORDS: Vasodilator Agents

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Gender-specific difference in cardiac ATP-sensitive K(+) channels. Information

Substance Name: Mixed Function Oxygenases

Registry Number: EC 1.-

Grant and Affiliation Information for Gender-specific difference in cardiac ATP-sensitive K(+) channels.

AFFILIATION: Tayside Institute of Child Health, Ninewells Hospital & Medical School, University of Dundee, Dundee, Scotland, United Kingdom.

Country: United States

AGENCY: United Kingdom British He

GRANT: PG/02/091/14227

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MEDLINETA: J Am Coll Cardiol

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