Effects of Total Replacement of Atrial Myosin Light
Chain-2 With the Ventricular Isoform in Atrial Myocytes of
Transgenic Mice
Corinn M. Pawloski-Dahm, PhD; Guojie Song, MD, PhD; Darryl L. Kirkpatrick, BS;
Joe Palermo, PhD; James Gulick, MS; Gerald W. Dorn II, MD;
Jeffrey Robbins, PhD; Richard A. Walsh, MD
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Background—In contrast to their well-known and critical role in excitation-contraction coupling of vascular smooth
muscle, the effects of the myosin light chains on cardiomyocyte mechanics are poorly understood. Accordingly, we
designed the present experiment to define the cardiac chamber–specific functional effects of the ventricular isoform of
the regulatory myosin light chain (MLC2v).
Methods and Results—Postnatal transgenic cardiac-specific overexpression of MLC2v was achieved by use of the
a-myosin heavy chain promoter. Enzymatically disaggregated atrial and ventricular mouse myocytes were fieldstimulated at multiple frequencies, and mechanical properties and calcium kinetics were studied by use of video edge
detection and FURA 2-AM, respectively. MLC2v overexpression resulted in complete replacement of the atrial with the
ventricular isoform of the regulatory myosin light chain at the steady-state mRNA and protein levels in the atria of
transgenic mice. Mechanical properties of transgenic atrial myocytes were enhanced to the level of ventricular myocytes
of control animals in association with modest decreases in the amplitude of the calcium transient.
Conclusions—MLC2v modulates chamber-specific contractility by enhanced calcium sensitivity and/or improved
cross-bridge cycling of the thin and thick filaments of the cardiomyocyte. (Circulation. 1998;97:1508-1513.)
Key Words: genes n myocytes n myosin
I
t has long been recognized that contraction of the heart is
dependent on the force generated by the interactions
between the thick and thin filaments of the cardiac sarcomere.
Detailed structural studies have demonstrated that force
generation in muscle cells is due to cross-bridge cycling
between thin-filament actin and thick-filament myosin
prompted by ATP hydrolysis.1–3 Myosin is a hexameric
molecule composed of two heavy-chain proteins and two
pairs of distinct light-chain proteins. There are two classes of
MLCs, and one of each is associated with each heavy chain.
Both types of MLC are usually encoded by a multiple gene
family, giving rise to a number of isoforms in each class that
are regulated in a tissue- and cardiac chamber–specific
fashion during development and pathological processes. The
two heavy chains each form a head region that contains the
ATP binding site and an a-helical tail region, whereas MLC1
and MLC2 are situated in the neck region of the myosin
heavy chain proteins. Data from more recent structural
studies provide evidence that it is small conformational
changes in the light chain binding regions that are responsible
for the actual movement of smooth muscle myosin with the
release of ADP.1–3 Although the structural relationship of the
MLC proteins to the contractile apparatus of muscle is
becoming clearer, the functional role of the light chain
proteins and their isoforms in muscle contraction is incompletely understood. In particular, less is known regarding the
role of the cardiac MLCs in excitation-contraction coupling
than is the case for these proteins in skeletal and smooth
muscle.
MLC2 is also called the regulatory light chain, because
phosphorylation of this protein controls contraction in smooth
muscle. In skeletal muscle, phosphorylation of MLC2 is
thought to have a modulatory role in both the rate and
magnitude of force generation.4 –9 In contrast, little is known
about the role of MLC2 and its phosphorylation in cardiac
myocyte shortening, although it has been demonstrated that
cardiac MLC2 phosphorylation produces a dramatic increase
in the sensitivity of tension development to increasing extracellular Ca21 concentrations.10 In addition, Damron et al11
reported that increased phosphorylation of MLC2 with endothelin or arachidonic acid treatment produced a positive
inotropic effect, which they interpreted as being consistent
with an increase in calcium sensitivity; however, calcium
transient data were not reported in that study. Thus, the role
Received August 22, 1997; revision received October 29, 1997; accepted November 7, 1997.
From the Department of Medicine, Division of Cardiology (C.M.P.-D., G.S., D.L.K., G.W.D., R.A.W.), and Department of Pediatrics, Division of
Molecular Cardiovascular Biology (J.P., J.G., J.R.), University of Cincinnati Medical Center, 231 Bethesda Ave, Cincinnati, Ohio.
Reprint requests to Richard A. Walsh, MD, Division of Cardiology, University of Cincinnati, PO Box 670542, Cincinnati, OH 45267-0542.
E-mail [email protected]
© 1998 American Heart Association, Inc.
1508
Pawloski-Dahm et al
MLC
MLC1
MLC2
MLC2a
MLC2v
Selected Abbreviations and Acronyms
5 myosin light chain
5 essential myosin light chain
5 regulatory myosin light chain
5 atrial isoform of regulatory myosin light chain
5 ventricular isoform of regulatory myosin light chain
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of MLC2 in a phosphorylated or dephosphorylated state in
cardiac muscle contraction is unclear. The cardiac regulatory
MLCs exist in chamber-specific isoforms for the atria
(MLC2a) and ventricles (MLC2v). Although these isoforms
arise from distinct genes and are altered in pathological states,
assigning different functional roles for the encoded proteins
has not been possible.
Recently, Palermo et al12 produced a transgenic mouse with
cardiac-specific postnatal overexpression of MLC2v. Although large increases in mRNA for MLC2v were seen in
both the atria and ventricles of the transgenic mouse heart, no
difference was observed in the total MLC2 protein in either
compartment. However, ectopic expression of MLC2v in the
atria resulted in the total replacement of the atrial isoform of
MLC2 by MLC2v. A similar phenomenon has been reported
in experimental and clinical cardiomyopathies.13–17 For instance, Kumar et al13 reported mRNA expression of MLC2v
in the atria of the spontaneously hypertensive rat, and an
increase in MLC2v protein has been reported in the atria of
humans with various cardiomyopathies.15,16 Because the atria
and ventricles of the heart play much different roles in cardiac
function (the ventricles are required to generate much greater
forces per beat than the atria), we hypothesized that replacement of the atrial isoform with the ventricular species would
result in functional changes at the myocyte level. To test this
hypothesis, the present experiments were designed to study
the contractile properties and intracellular calcium kinetics of
enzymatically isolated atrial and ventricular myocytes derived from a transgenic mouse line that overexpresses
MLC2v.
Methods
Animals
Transgenic mice12 with postnatal cardiac-specific overexpression of
MLC2v and nontransgenic control mice were used as sources of isolated
myocytes. All mice were studied between 11 and 13 weeks of age, and
equal distributions of male and female mice were used in each group.
Mouse ventricular myocytes were isolated by methods previously
reported for this laboratory unless otherwise noted.18 –20 Transgenic mice
were identified by PCR analysis of DNA isolated from tail clips.
Isolation of Ventricular Myocytes
Mice were anesthetized with methoxyflurane, hearts were quickly
excised, and the aortas were cannulated with a blunted 23-gauge
needle, flushed with buffer (MEM, Joklik-modified, pH 7.2; Gibco
BRL), and mounted onto a Langendorff perfusion apparatus. Ventricular myocytes were isolated from hearts of control and transgenic
mice by methods slightly modified from those described previously.18,19 Briefly, all perfusates were maintained at 37°C and continuously bubbled with 95%O2/5%CO2. The coronary arteries were
perfused retrogradely at 2.2 mL/min initially with calcium-free
Joklik buffer (4 minutes), followed by Joklik buffer supplemented
with 0.25 mmol/L Ca21, 75 U/mL collagenase I (Worthington), 75
U/mL collagenase II (Worthington), 1% BSA (Sigma), and 2%
April 21, 1998
1509
donor calf serum (pH 7.2). After '12 to 15 minutes, the heart was
removed from the perfusion apparatus and transferred to a glass dish
containing Joklik buffer supplemented with 0.25 mmol/L Ca21 and
2% donor calf serum. The left ventricle was isolated from the rest of
the chambers and minced, and isolated cells were washed and
resuspended in a physiological buffer (in mmol/L: NaCl 132, KCl
4.8, MgCl2 z 6H2O 1.2, glucose 5, and HEPES 10, pH 7.2)
supplemented with 1.8 mmol/L calcium for study.
For atrial myocyte isolation, hearts were perfused by the same
methods as described above for ventricular cell isolation. However,
once atrial tissue was removed from the rest of the heart, cells were
isolated by gentle teasing of the tissue with hypodermic needles in a
glass dish with enzyme-free low-calcium Joklik medium. If cells did
not easily separate from tissue pieces, the tissue was allowed to soak
in enzyme solution for 5 to 10 minutes, as needed. Cells were then
allowed to settle in a tube before the Joklik medium was removed
and replaced with physiological buffer as described above.
Mechanical Properties18 –20
For measurements of morphological and mechanical properties of
isolated myocytes, cells were placed in a well on the stage of an
inverted microscope and were perfused continuously with oxygenated physiological buffer. Two platinum electrodes connected to a
Grass model S9 stimulator were placed on either side of an identified
healthy-appearing, rod-shaped myocyte with clearly visible striations
and no evidence of blebbing. Myocytes were field-stimulated at
varying frequencies (0.25, 0.5, and 1.0 Hz; 5-ms pulse duration) for
at least 40 seconds per pacing rate. Cell images were acquired
continuously through a charge-coupled device (model GP-CD60)
and recorded on videotape. With a video motion edge detector
(Crescent Electronics), these videotaped images were then captured
on a Gould chart recorder from which percent shortening and rates of
shortening (1dL/dt) and relengthening (2dL/dt) were quantified by
comparison with a calibrated micrometer on the microscope stage.
Calcium Measurements18 –20
Once left ventricular cells were isolated, half were used for mechanical
studies and the other half for the calcium kinetic studies. In contrast, for
the assessment of atrial cell function, the entire left atrium was required,
so separate mice were used for mechanical and calcium measurements.
Disaggregated myocytes were placed in FURA 2-AM (ventricular cells,
7.5 mmol/L and atrial cells, 2.5 mmol/L) and incubated at 37°C for '15
minutes in the dark. After FURA loading of cells was completed, the
cells were then suspended in physiological buffer as described above.
Cytosolic free calcium was measured in mouse myocytes by ratio
imaging of 340 to 380 nm fluorescence of FURA 2 (emission wavelength, 510 nm) with a photo scan dual-beam spectrofluorophotometer
(Photon Tech, Inc) coupled to an Olympus IMT-2 UV fluorescent
microscope with UV transparent optics. Cells underwent a pacing
protocol similar to that performed in the mechanical studies, and
baseline and peak intracellular calcium transients were measured in
response to changes in stimulation frequencies.
Statistical Analyses
At least three cells were examined per mouse, per chamber (atrium
and ventricle), and the values were averaged for mechanical parameters and Ca21 kinetics. Statistical analysis is based on the number of
animals rather than the number of cells. Data are expressed as
mean6SEM and are analyzed by two-way ANOVA followed by the
Student-Newman-Keuls test for individual post hoc comparisons.
Morphological data were analyzed by unpaired t test. If data were not
normally distributed or failed equal variance tests after log10 transformations, they were analyzed by nonparametric statistics (ie, either
Kruskal-Wallis for ANOVA designs or Mann-Whitney rank sum test
for comparison between two groups of data). A value of P,.05 was
set as the criteria for statistical significance.
Results
Morphological and Mechanical Properties of
Mouse Ventricular Myocytes
Ventricular myocytes isolated from transgenic mice were
morphologically indistinct from control ventricular myocytes
1510
MLC2v in Atrial Myocytes of Mice
TABLE 1.
Ventricular and Atrial Myocyte Mechanical Properties With Changes in Pacing Rates
Pacing Rate, bpm
Ventricular Myocytes
Atrial Myocytes
15
30
60
15
30
60
C
13.361.8
11.661.9
11.162.0
6.660.5†
5.560.5†
5.060.4†
Tg
10.062.1
9.062.1
8.562.2
13.762.2*
12.662.2*
12.262.2*
C
270.6627.2
243.4627.9
245.9635.2
122.5614.2†
102.4612.6†
106.5615.3†
Tg
148.8620.5*
140.5620.8*
135.3620.1*
218.7631.9*
201.0623.7*
206.1621.8*
C
171.0615.4
166.1619.3
160.5626.9
93.869.5†
83.569.0†
Tg
102.7617.6*
155.9620.5*
155.1624.0*
% Shortening
1dL/dt, mm/s
2dL/dt, mm/s
94.5615.4*
91.0613.3*
87.5611.0†
163.9621.4*
Cell width, mm
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C
40.764.3
21.062.8†
Tg
30.462.7
17.561.0†
Cell length, mm
C
105.366.8
75.62.9†
Tg
98.466.7
60.364.7*†
C
0.4060.06
0.2760.07
Tg
0.3160.06
0.2960.02
Width/length
C indicates control, n56; Tg, transgenic, n56. Values are mean6SEM.
*P,.05 vs C.
†P,.05 vs ventricular myocytes.
(Table 1). Representative analog tracings of myocyte shortening (Fig 1) demonstrate that the extent of ventricular
myocyte shortening measured in these cells was not different
between transgenic and control mice at any of the three
stimulation frequencies. However, the rates of shortening
(1dL/dt) and relengthening (2dL/dt) produced by electrical
stimulation of the myocytes at each pacing rate were diminished in the transgenic ventricular myocytes compared with
control cells. These findings are confirmed by the composite
Figure 1. Representative analog recordings of mouse ventricular (left) and atrial (right) myocyte mechanics from a control (top)
and an MLC2v overexpression transgenic (bottom) mouse. Phasic cell length is in micrometers as determined by edge detection, and the first derivative of cell shortening and relengthening,
dL/dt, is in mm/s.
data as illustrated in Table 1 and Fig 2. Thus, with no
detectable difference in total MLC2v protein levels between
mice, transgenic ventricular myocytes demonstrated similarities in percent shortening but depressed rates of contraction
and relaxation.
Morphological and Mechanical Properties of
Mouse Atrial Myocytes
Atrial myocytes isolated and studied from transgenic mice
with cardiac-specific ectopic replacement of the atrial with
the ventricular isoform of MLC2 in the heart were significantly shorter than atrial myocytes similarly isolated from
nontransgenic littermates (Table 1). Compared with ventricular myocytes, atrial myocytes were shorter and thinner in
both groups (Table 1). However, no differences were seen in
cell width-to-length ratios between either atrial and ventricular myocytes or atrial cells isolated from control versus
those from transgenic mice. When electrically stimulated at
incremental pacing frequencies, control atrial myocytes exhibited a much attenuated percent shortening compared with
transgenic atrial or control ventricular myocytes (Table 1;
Figs 1 and 2). Similarly, rates of shortening and relengthening
in control atrial myocytes were much less than those in either
transgenic atrial or control ventricular cells (Table 1, Fig 2).
These findings were similar at all three stimulation frequencies. Furthermore, comparisons of contractile properties
within groups were not significantly different with increasing
pacing rates. In contrast to control atrial myocytes, the atrial
myocytes isolated from the mice in which MLC2v protein
Pawloski-Dahm et al
April 21, 1998
1511
explained by differences in intracellular Ca21 kinetics (Table
2). Baseline and peak Ca21 levels obtained during electrical
pacing of myocytes were not different between ventricular
cells isolated from control and transgenic mice. In addition,
the times of 50% (T50) and 80% (T80) Ca21 signal decay were
similar between groups. Altering the pacing frequencies
affected neither the intergroup group relationships nor intragroup group comparisons of the Ca21 kinetics.
Intracellular Ca21 Measurements in Mouse
Atrial Myocytes
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Baseline Ca21 levels and Ca21 signal amplitudes for atrial
myocytes paced at three pacing rates are shown in Table 2. As
was seen with ventricular myocytes isolated from transgenic
mice, atrial myocytes from these mice demonstrated baseline
Ca21 signals similar to atrial cells taken from nontransgenic
mice. The amplitude of the Ca21 signals was slightly but
significantly lower in the transgenic atrial myocytes than in
control cells. Furthermore, although baseline signals were not
different between ventricular and atrial myocytes, the amplitude of the Ca21 signals produced by electrical pacing of the
cells was significantly lower in the atrial than in the ventricular myocytes in both groups of mice.
Figure 2. Group data for mechanical properties of ventricular
(vent) and atrial myocytes isolated from control (c) and transgenic (tg) mice with cardiac-specific overexpression of MLC2v.
A, Extent of cell shortening (% Shortening). B, Rate of shortening (1dL/dt, mm/s). C, Rate of relengthening (2dL/dt, mm/s).
Data are mean6SEM. *P,.05 vs c; #P,.05 vs vent.
had completely replaced the atrial isoform of MLC2 demonstrated contractile properties that were similar to those of
nontransgenic ventricular myocytes (Fig 1).
Intracellular Ca21 Measurements in Mouse
Ventricular Myocytes
The differences in rates of contraction and relaxation between
transgenic and control ventricular myocytes could not be
TABLE 2.
Discussion
The present studies report, for the first time, the mechanical
properties and calcium kinetics of atrial myocytes derived
from the mouse heart. These data demonstrate that isolated
unloaded mouse atrial myocytes contract to a lesser extent
and at slower rates than do isolated ventricular cells. However, total replacement of the atrial isoform of MLC2 by the
ventricular isoform in the atria of the mouse results in atrial
cells that contract and relax at greater rates and to a greater
extent than do isolated atrial cells from control mice. In fact,
the transgenic atrial myocytes demonstrate contractile properties similar to normal ventricular cells. These studies also
Calcium Kinetics of Isolated Ventricular and Atrial Myocytes With Changes in Pacing Rates
Pacing Rate, bpm
Ventricular Myocytes
15
Atrial Myocytes
30
60
15
30
60
Baseline, 340/380 unit
C
1.1060.12
1.1960.12
1.2360.12
0.9660.12
1.0160.12
1.1260.09
Tg
1.1260.09
1.0560.10
1.1160.10
0.9460.11
1.0060.12
1.0460.11
C
1.2860.32
1.2960.25
1.3560.10
0.5960.05†
0.4660.07†
0.3460.04†
Tg
1.4760.37
1.1760.34
0.8760.23
0.3160.06*†
0.2760.06*†
0.2060.06†
C
0.336.04
0.3060.02
0.2760.04
0.6560.09†
0.5760.05†
0.4360.04†
Tg
0.3260.04
0.2960.02
0.2560.02
0.7460.04†
0.5960.03†
0.4460.01†
Amplitude, 340/380 unit
T50, s
T80, s
C
0.6560.08
0.5860.02
0.4260.03
1.0860.18†
0.8960.09†
0.5660.05†
Tg
0.6460.12
0.6060.08
0.4660.05
1.3360.07†
0.9660.04†
0.5960.02†
C indicates control, n54; Tg, Transgenic, n54. Values are mean6SEM.
*P,.05 vs C.
†P,.05 vs ventricular myocytes.
1512
MLC2v in Atrial Myocytes of Mice
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demonstrate that although baseline Ca21 transients are not
different between control and transgenic cells, normal atrial
myocytes exhibit lower Ca21 signal amplitudes than do
ventricular myocytes and transgenic atrial cells have lower
amplitudes than do atrial cells from nontransgenic mice.
These data suggest that the regulatory MLCs can play a major
role in the differentiation of cardiac compartment muscle
mechanics and calcium signaling and that chamber-specific
isoforms have unique functional properties.
The atrial-to-ventricular switch of MLC2 occurs during
postnatal development of the ventricle in response to the
accompanying changes in intra-atrial pressures.13,17 On the
basis of the present studies, the postnatal MLC isoform
switch in the left ventricle of the neonate may facilitate
ejection against the increased systemic arterial pressure that
occurs at parturition. In addition, several studies have demonstrated expression of the ventricular isoform of MLC2 in
the atria of hypertrophied hearts of both humans and experimental animals in response to pathological conditions.13–17
Wanker et al15 found MLC2v in atrial samples from patients
with a variety of cardiomyopathies, and the level of ventricular isoform expression correlated with the severity of heart
failure. Likewise, Cummins16 reported that the degree of
pressure-overload hypertrophy in humans is the most significant factor influencing ventricular MLC2v isoform expression in the human atria. Just as in the developing neonatal
ventricle, it was hypothesized that the changes in atrial
chamber pressures were responsible for this isoform switch in
myopathic atria. However, Kumar et al13 demonstrated that
the atria from the spontaneously hypertensive rat had greater
levels of MLC2v mRNA expression than did atria from
age-matched normotensive Wistar-Kyoto rats that preceded
the development of both hypertension and cardiac hypertrophy. These studies are inconsistent with the hypothesis that
the atrial-to-ventricular switch of MLC2 in the atria occurs
solely as a result of hemodynamic factors. Therefore, although there may be some relationship between cardiomyopathy and the atrial-to-ventricular MLC2 switch in the atria, it
remains unknown whether this phenomenon plays a role in or
is a consequence of the pathological condition. Furthermore,
it is unknown how this switch affects atrial as well as
ventricular function. Data from the present studies suggest
that enhanced atrial expression of MLC2v in the diseased
heart may be a compensatory mechanism to maintain and
enhance the left atrial contribution to ventricular filling.
The present studies demonstrate that mechanical properties
of mouse atrial myocytes that ectopically express MLC2v are
similar to ventricular myocytes. It appears that the only
biochemical difference between the nontransgenic and transgenic left atria is the total replacement of the atrial MLC2
isoform by the ventricular MLC2 isoform. Transgenic atrial
MLC2v has a higher basal phosphorylation level than
MLC2v in the ventricles. In addition, there was also no
difference in the degree of phosphorylation between the
wild-type and transgenic atrial MLC2.21 Thus, the altered
mechanical properties of the transgenic atrial myocytes appear to be unrelated to any change in the level of phosphorylation brought about by the atrial-to-ventricular MLC2
isoform switch. In addition, there are no differences in the
myosin heavy chain isoforms, the major determinant of
myosin ATPase activity, in the calcium-cycling proteins (the
sarcoplasmic reticulum ATPase and phospholamban) or in
a-actin isoform composition between the atria of wild-type
and transgenic mice.21 We therefore consider it a reasonable
hypothesis that the morphological differences (shorter atrial
myocytes) as well as mechanical differences (greater percent
shortening and faster rates of shortening and relengthening)
in the transgenic atrial myocyte are a direct consequence of
the regulatory MLC isoform replacement. The cell length
differences could not have been observed or predicted from
previously performed in vitro motility assays and are difficult
to explain on the basis of current understanding of structural
relationships of myosins in cardiac muscle. However, these
data imply that MLC2 plays an important role in determining
the contractile properties of the cardiac chambers.
Depressed mechanical function of nontransgenic atrial
myocytes compared with ventricular cells might be predicted
from the calcium kinetic studies. Increased intracellular Ca21
levels and lower T50 and T80 in the ventricular myocytes
compared with atrial myocytes support the mechanical data
that unloaded ventricular cells contract faster and to a greater
extent than do atrial cells. However, compared with nontransgenic atrial cells, transgenic atrial myocytes exhibit slightly
lower electrically stimulated increases in intracellular Ca21,
with no differences in T50 or T80. Thus, the increase in atrial
myocyte contractility in transgenic mice compared with
wild-type atrial myocyte shortening resulting from replacement of the atrial with the ventricular isoform of the regulatory MLC cannot be explained on the basis of altered calcium
kinetics. It appears that the ventricular MLC isoform switch
enhances atrial cardiomyocyte calcium sensitivity of the
myofilament and/or facilitates more effective actin-myosin
cross-bridge development and cycling.
On the basis of the biochemical analyses of the transgenic
ventricles (ie, no difference in MLC2v protein expression
between control and transgenic),12 no difference in mechanical properties would be predicted between the left ventricular
myocytes of these groups. There was no difference in the
gross morphology of the ventricular myocytes. However,
modest but statistically significant slower rates of shortening
and relengthening of transgenic ventricular myocytes were
observed. The reasons for depressed mechanical function in
the transgenic ventricular myocytes are not readily apparent.
These differences cannot be explained on the basis of altered
phosphorylation status, myosin heavy chain isoform composition, calcium-cycling proteins, or a-actin isoform composition between wild-type and transgenic ventricles.21 It has been
postulated that heart rate plays a role in the activity of MLC
kinase, the enzyme responsible for phosphorylation of
MLC2.7,10 However, neither conscious heart rates nor phosphorylation status differed between wild-type and transgenic
mice.21 One possibility for the mildly depressed function of
the transgenic ventricular myocytes is that there may be other
biochemical changes not yet established, either as a result of
the enhanced mechanical properties of the atria or simply
endogenous to this transgenic line. What is clear from the
present experiments is that the depressed mechanical proper-
Pawloski-Dahm et al
ties of the transgenic ventricular myocytes are not due to
changes in intracellular calcium handling.
In conclusion, these data demonstrate that total replacement of the atrial isoform of MLC2 with the ventricular
isoform in the left atrium of the mouse results in atrial
myocytes with mechanical and morphological properties
similar to those of ventricular cells, despite modestly diminished intracellular calcium transients. These studies suggest
that MLC2 isoforms in cardiac tissue are central to the
differential contractility of compartmentalized heart muscle.
Further study of these transgenic mice might lead to an even
greater understanding of the role of MLC2v in cardiac muscle
contraction under normal conditions, as well as the role of its
expression in the atria observed in cardiomyopathies.
Acknowledgment
This work was supported in part by SCOR in Heart Failure grant
HL-52318 from the National Heart, Lung, and Blood Institute.
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Effects of Total Replacement of Atrial Myosin Light Chain-2 With the Ventricular Isoform
in Atrial Myocytes of Transgenic Mice
Corinn M. Pawloski-Dahm, Guojie Song, Darryl L. Kirkpatrick, Joe Palermo, James Gulick,
Gerald W. Dorn II, Jeffrey Robbins and Richard A. Walsh
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Circulation. 1998;97:1508-1513
doi: 10.1161/01.CIR.97.15.1508
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