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© 2001 American Heart Association, Inc.
Cellular Biology |
Decreased Expression of Voltage- and Ca2+-Activated K+ Channels in Coronary Smooth Muscle During Aging
From the Departments of Anesthesiology (J.M., Q.X.L., M.S., K.N., E.S., L.T.), Molecular & Medical Pharmacology (L.T.), and Physiology (E.S.), and the Brain Research Institute (E.S., L.T.), University of California Los Angeles, Los Angeles, Calif. The present affiliation for Q.X.L. is the House Ear Institute, Los Angeles, Calif.
Correspondence to Ligia Toro, Department of Anesthesiology, UCLA, BH-509A CHS, Box 957115, Los Angeles, CA 90095-7115. E-mail ltoro{at}ucla.edu
Abstract—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 Ca2+-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 
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 
50%. Moreover, the age-related decrease in the
channel protein expression was also evident in humans, which showed
80% reduction in 61- to 70-year-old subjects compared with 3- to
18-year-old youngsters and 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 (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.
Key Words: vascular smooth muscle • coronary arteries • K+ channels • Ca2+-activated K+ channels • aging
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