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(Circulation. 1995;92:164-174.)
© 1995 American Heart Association, Inc.
Articles |
Characterization of Inwardly Rectifying K+ Channel in Human Cardiac Myocytes
Alterations in Channel Behavior in Myocytes Isolated From Patients With Idiopathic Dilated Cardiomyopathy
From the Division of Cardiology (S.-i.K.), Department of Medicine, and the Feinberg Cardiovascular Research Institute; and the Department of Surgery (C.L.B., C.E.A.), Northwestern University School of Medicine, Chicago, Ill.
Correspondence to Shin-ichi Koumi, MD, PhD, Department of Medicine, Hazaki Saiseikai Hospital, 8968 Hazaki, Kashimagun, Ibaragi 314-04, Japan.
Background Little is known about the characteristics of the inwardly rectifying K+ channel (IK1) and the influence of preexisting heart disease on the channel properties in the human heart.
Methods and Results We studied the characteristics of cardiac
IK1 in freshly isolated adult human atrial and
ventricular myocytes by using the patch-clamp technique.
Specimens were obtained from the atria and ventricles of 48 patients
undergoing cardiac surgery or transplantation and from four explanted
donor hearts. The action potential in ventricular myocytes
exhibited a longer duration (391.4±30.2 milliseconds at 90%
repolarization, n=10) than in atrium (289.4±23.0 milliseconds,
n=18,
P<.001) and had a fast late repolarization phase (phase 3).
The final phase of repolarization in ventricle was frequency
independent. Whole-cell IK1 in ventricle
exhibited greater slope conductance (84.0±7.9 nS at the reversal
potential, EK; n=27) than in atrium (9.7±1.2 nS at
EK; n=8, P<.001). The steady-state
current-voltage (I-V) relation in ventricular
IK1 demonstrated inward rectification with a
region of negative slope. This negative slope region was not prominent
in atrial IK1. The macroscopic currents were
blocked by Ba2+ and Cs+. The channel
characteristics in ventricular myocytes from patients with
congestive heart failure after idiopathic dilated
cardiomyopathy (DCM) exhibited distinct properties
compared with those from patients with ischemic
cardiomyopathy (ICM). The action potential in
ventricular myocytes from patients with DCM had a longer
duration (490.8±24.5 milliseconds, n=11) compared with that for
ICM
(420.6±29.6 milliseconds, n=11, P<.01) and had a
slow
repolarization phase (phase 3) with a low resting membrane potential.
The whole-cell current slope conductance for DCM was smaller (41.2±9.0
nS at EK, n=7) than that for ICM (80.7±17.0 nS,
n=6, P<.05). In single-channel recordings from
cell-attached patches, ventricular
IK1 channels had characteristics similar to
those of atrial IK1; channel openings occurred
in long-lasting bursts with similar conductance and gating kinetics. In
contrast, the percent of patches in which IK1
channels were found was 34.7% (25 of 72) of patches in atrium and
88.6% (31 of 35) of patches in ventricle. Single
IK1 channel activity for DCM exhibited frequent
long-lasting bursts separated by brief interburst intervals at every
holding voltage with the open probability displaying little voltage
sensitivity (
0.6). Channel activity was observed in 56.2% (18 of
32) of patches for DCM and 77.4% (24 of 31) of patches for ICM.
Similar results were obtained from atrial IK1
channels for DCM. In addition, channel characteristics were not
significantly different between ICM and explanted donor hearts
(donors). IK1 channels in cat and guinea pig had
characteristics virtually similar to those of humans, with the
exception of lower open probability than that in humans.
Conclusions These results suggest that the electrophysiological characteristics of human atrial and ventricular IK1 channels were similar to those of other mammalian hearts, with the possible exception that the channel open probability in humans may be higher, that the whole-cell IK1 density is higher in human ventricle than in atrium, and that IK1 channels in patients with DCM exhibited electrophysiological properties distinct from IK1 channels found in patients with ICM and in donors.
Key Words: potassium • myocytes • cardiomyopathy
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