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Vascular Cell Biology Laboratory, Dalton Cardiovascular Research Center, and Departments of Physiology and Veterinary Biomedical Sciences, University of Missouri, Columbia, Missouri 65211
Heterogeneity of vascular responses to
physiological and pharmacological stimuli has been demonstrated
throughout the coronary circulation. Typically, this heterogeneity is
based on vessel size. Although the cellular mechanisms for this
heterogeneity are unknown, one plausible factor may be heterogeneous
distribution of ion channels important in regulation of vascular tone.
Because of the importance of voltage-gated
Ca2+ channels in regulation of
vascular tone, we hypothesized that these channels would be unequally
distributed throughout the coronary arterial bed. To test this
hypothesis, voltage-gated Ca2+
current was measured in smooth muscle from conduit arteries (>1.0 mm), small arteries (200-250 µm), and large arterioles
(75-125 µm) of miniature swine using whole cell voltage-clamp
techniques. With 2 mM Ca2+ or 10 mM Ba2+ as charge carrier,
voltage-gated Ca2+ current density
was inversely related to arterial diameter, i.e., large arterioles > small arteries > conduit. Peak inward currents (10 mM
Ba2+) were increased ~2.5- and
~1.5-fold in large arterioles and small arteries, respectively,
compared with conduit arteries (
5.58 ± 0.53,
3.54 ± 0.34, and
2.26 ± 0.31 pA/pF, respectively). In physiological Ca2+ (2 mM), small
arteries demonstrated increased inward current at membrane potentials
within the physiological range for vascular smooth muscle (as negative
as
40 mV) compared with conduit arteries. In addition, cells
from large arterioles showed a negative shift in the membrane potential
for half-maximal activation compared with small and conduit arteries
(
13.23 ± 0.88,
6.22 ± 1.35, and
8.62 ± 0.81 mV, respectively; P < 0.05).
Voltage characteristics and dihydropyridine sensitivity identified this
Ca2+ current as predominantly
L-type current in all arterial sizes. We conclude that L-type
Ca2+ current density is inversely
related to arterial diameter within the coronary arterial vasculature.
This heterogeneity of Ca2+ current
density may provide, in part, the basis for functional heterogeneity
within the coronary circulation.
voltage clamp; dihydropyridine; vascular smooth muscle
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