Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-22
pubmed:abstractText
Aging is the main risk factor for coronary artery disease. One characteristic of aging coronary arteries is their enhanced contractile responses to endothelial vasoconstricting factors, which increase the risk of coronary vasospasm in older people. Because large-conductance voltage- and Ca(2+)-activated K(+) channels (MaxiK) are key regulators of vascular tone, we explored the possibility that this class of channels is diminished with increasing age. Using site-directed antibodies recognizing the pore-forming alpha subunit and electrophysiological methods, we demonstrate that the number of MaxiK channels is dramatically diminished in aged coronary arteries from old F344 rats. Channel density was reduced from 52+/-9 channels/pF (3 months old) to 18+/-5 channels/pF (25 to 30 months old), which represents a 65% reduction in the older population. Pixel intensity of Western blots was also diminished by approximately 50%. Moreover, the age-related decrease in the channel protein expression was also evident in humans, which showed approximately 80% reduction in 61- to 70-year-old subjects compared with 3- to 18-year-old youngsters and approximately 45% reduction compared with 19- to 56-year-old adults. In agreement with a reduction of MaxiK channel numbers in aging coronary arteries, old coronary arteries from F344 rats contract less effectively ( approximately 70% reduction) than young coronary arteries when exposed to the MaxiK channel blocker iberiotoxin. The contraction studies indicate that under physiological conditions, MaxiK channels are tonically active, serving as a hyperpolarizing force that opposes contraction. Thus, reduced expression of MaxiK channels in aged coronary arteries would lead to a decreased vasodilating capacity and increased risk of coronary spasm and myocardial ischemia in older people.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1524-4571
pubmed:author
pubmed:issnType
Electronic
pubmed:day
2
pubmed:volume
88
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
210-6
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:11157674-Adolescent, pubmed-meshheading:11157674-Adult, pubmed-meshheading:11157674-Age Distribution, pubmed-meshheading:11157674-Aging, pubmed-meshheading:11157674-Animals, pubmed-meshheading:11157674-Calcium, pubmed-meshheading:11157674-Coronary Vessels, pubmed-meshheading:11157674-Dose-Response Relationship, Drug, pubmed-meshheading:11157674-Female, pubmed-meshheading:11157674-Humans, pubmed-meshheading:11157674-Immunohistochemistry, pubmed-meshheading:11157674-Isometric Contraction, pubmed-meshheading:11157674-Large-Conductance Calcium-Activated Potassium Channel..., pubmed-meshheading:11157674-Large-Conductance Calcium-Activated Potassium Channels, pubmed-meshheading:11157674-Male, pubmed-meshheading:11157674-Middle Aged, pubmed-meshheading:11157674-Muscle, Smooth, Vascular, pubmed-meshheading:11157674-Patch-Clamp Techniques, pubmed-meshheading:11157674-Peptides, pubmed-meshheading:11157674-Potassium Channel Blockers, pubmed-meshheading:11157674-Potassium Channels, pubmed-meshheading:11157674-Potassium Channels, Calcium-Activated, pubmed-meshheading:11157674-Rats, pubmed-meshheading:11157674-Rats, Inbred F344, pubmed-meshheading:11157674-Vasoconstriction
pubmed:year
2001
pubmed:articleTitle
Decreased expression of voltage- and Ca(2+)-activated K(+) channels in coronary smooth muscle during aging.
pubmed:affiliation
Department of Anesthesiology, University of California Los Angeles, Los Angeles, CA 90095-7115, USA.
pubmed:publicationType
Journal Article, In Vitro, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't