© 2001 American Heart Association, Inc.
Editorials |
Potassium Ions as Vasodilators: Role of Inward Rectifier Potassium Channels
From the Department of Pharmacology, University of Vermont College of Medicine, Burlington, Vt.
Correspondence to Mark T. Nelson, PhD, Department of Pharmacology, Given Building, B326, University of Vermont College of Medicine, Burlington, VT 05405. E-mail nelson{at}salus.med.uvm.edu
Key Words: kidney • afferent arteriole • potassium channels • renal arterioles
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Introduction |
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 Top Introduction References |
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External potassium ions have long been known as mediators of vasodilation of several vascular beds, including the coronary and cerebral circulations.1 2 3 4 5 6 Indeed, potassium ions have been viewed as communicators of the metabolic state of the cells that surround blood vessels. For example, release of potassium ions from neurons is communicated through glial cells to regulate cerebral artery diameter.7 Recently, it has been suggested that the potassium ions from endothelial cells may signal smooth muscle to relax and, as such, may constitute an endothelial-derived hyperpolarizing factor.8
Two targets of external potassium ions have been proposed:
the Na+/K+ ATPase
and the inward rectifier potassium
channel.1 5 9
An elevation of external potassium causes very different responses of
these two molecular targets. The electrogenic
Na+/K+ ATPase is
activated by external potassium with a half-activation constant of
about 1 to 2 mmol/L10 and
saturation above 5
mmol/L.11 12
Activation of the
Na+/K+ ATPase by
elevating external potassium from nominally 0 to 5 mmol/L causes
transient hyperpolarization and
dilation5 ; the transient
nature presumably reflects the extrusion of sodium until a new steady
state is reached. In contrast, elevation of external potassium causes a
graded shift in the apparent voltage-dependence of the inward rectifier
potassium channel
conductance,13 which can
lead to a maintained hyperpolarization and
dilation.14 Unfortunately,
the dissection of these pathways until recently has relied on two
imperfect pharmacological probes: cardiotonic steroids, such as
ouabain, and barium ions. Inhibition of the
Na+/K+ ATPase
with ouabain leads to a membrane potential depolarization, an elevation
in intracellular sodium and calcium, and several other changes
downstream from these events. This complicates the interpretation of
ouabain effects, unless it has no effect on potassium-induced
hyperpolarization and
dilations.14 Barium ions
block inward rectifier potassium channels with a relatively high
affinity of 
10 µmol/L at physiological membrane
potentials.13 Nonetheless,
barium ions block other ion channels at higher concentrations. These
problems have been obviated by the use of inward rectifier knockout
mice, which have been shown to lack potassium-induced
dilations.15
Much of the research on potassium-induced dilations has
focused on the cerebral and coronary circulation. Small increases in
circulating potassium ions in vivo dilate and increase cerebral
flow.4 16 17
Recently, Chrissabolis et
al17 demonstrated that
cerebral artery dilations in vivo to elevated
K+ in cerebral spinal fluid were
Ba2+-sensitive and insensitive to ouabain,
strongly supporting a role for inward rectifier potassium channels. In
the cerebral vasculature, elevations in K+
ions increase with neuronal activity and during stresses such as
cerebral hypoxia, ischemia, and
hypoglycemia.7 16 18
K+-induced dilations have also been reported
in coronary arteries.1
K+ ions are normally released from cardiac
cells during increased workload and particularly under
ischemia.19 20 21
In the kidney, elevated potassium (10 mmol/L) or acute hyperkalemia
have been shown to increase renal blood flow and glomerular filtration
rate.22 23
In a study in this issue of
Circulation Research, Chilton
and Loutzenhiser24 have
explored the role of inward rectifier potassium channels in
K+-induced dilations of rat renal afferent
arterioles, using the hydronephrotic kidney model. This model permits
visualization of the renal microvasculature under normal flow and
pressure conditions. Loutzenhiser et
al25 have taken this model
one step further and developed a method for measuring stable membrane
potentials while simultaneously measuring diameter of intact afferent
arterioles in the intact kidney. In pressurized afferent arterioles,
increasing [K+]o
from 5 to 15 mmol/L resulted in
Ba2+-sensitive dilations. In the presence of
the 
-adrenoceptor blockers, K+-induced
dilations were also abolished by chloroethylclonidine (CEC). CEC has
been shown to inhibit native inwardly rectifying potassium channels
(Kir) in skeletal muscle (rat flexor digitorium brevis) as well as
Kir2.1 channels expressed in the MEL cell
line.26 Neither the
KATP channel inhibitor glibenclamide nor ouabain
inhibited K+-induced dilations in the
afferent arteriole. Ba2+ depolarized and
constricted afferent arterioles at low pressures, suggesting a role for
Kir channels in regulating membrane potential. The Chilton and
Loutzenhiser24 study, along
with studies on the cerebral and coronary
circulations,14 15 17 27
strongly supports the idea that the inward rectifier potassium channel,
in particular the Kir2.1
subtype,28 is a molecular
target for external potassium-induced
vasodilation.
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Footnotes |
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The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.
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References |
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TopIntroductionReferences |
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2.
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