Regional differences in the response of feline esophageal
smooth muscle to stretch and cholinergic stimulation
Ahmad
Muinuddin2,3,
Shuwen
Xue3, and
Nicholas E.
Diamant1,2,3
Departments of 1 Medicine and 2 Physiology,
University of Toronto, Toronto, Ontario M5S 1A8; and
3 Toronto Western Research Institute, University Health
Network, Toronto, Ontario M5T 2S8, Canada
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ABSTRACT |
There are no
objective differences in neural elements that explain regional
differences in neural influences along the smooth muscle (SM)
esophageal body (EB). Regional differences in muscle properties are
present in the lower esophageal sphincter (LES). This study examines
whether regional differences in SM properties exist along the EB and
are reflected in length-tension relationships and responses to
cholinergic excitation. Circular SM strips from feline EB at 1 cm (EB1)
and 3 cm (EB3) above LES and from clasp and sling muscle bundles of LES
were assessed in normal and calcium-free solutions with and without
bethanechol stimulation. Neural inhibition was assessed by electrical
field stimulation (EFS). EB3 developed significantly higher tension in
response to stretch and to bethanechol than did EB1. The relaxation
response to EFS in bethanechol-precontracted strips was less in EB3
than in EB1. In LES, clasp developed higher resting tension than sling
but less active tension in response to bethanechol. EFS-induced
relaxations of sling and clasp tissues precontracted by bethanechol
were not different. In calcium-free solution, length-tension
differences between EB3 and EB1 persisted, but those of LES clasp and
sling were abolished. Therefore, regional myogenic differences exist in
feline EB circular SM as well as in LES and may contribute to the
nature of esophageal contraction.
bethanechol; esophagus; length-tension relations; tetrodotoxin
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INTRODUCTION |
MOVEMENT OF THE
PERISTALTIC contraction along the smooth muscle esophagus has
been attributed to differences in the innervation along the esophagus.
There is a functional gradient in the nitregeric, nonadrenergic,
noncholinergic inhibitory influence (increasing distally) along the
opossum and cat esophagus (1, 33) and a functional
gradient in the cholinergic excitatory influence (decreasing distally).
The latter has been seen in the opossum but has not been convincingly
demonstrated in the cat (10). However, there are no
objective differences in neural elements relative to smooth muscle
content to explain the differing neural influences along the esophagus
(18, 19, 23, 26). On the other hand, significant
differences in the resting membrane potential and ion channel
activities have been recently demonstrated along the cat smooth muscle
esophagus (24). Therefore, regional differences in muscle
properties and responsiveness to the innervation present themselves as
additional or alternative explanations for the functional differences.
This raises the possibility that differing muscle properties along the
esophagus will dictate different responses of the smooth muscle itself
to neurotransmitters such as acetylcholine.
Differences in the cholinergic responses of smooth muscle from clasp
and sling regions of the lower esophageal sphincter (LES) and between
LES and esophageal body (EB) smooth muscle are known to exist. Studies
of the clasp and sling fibers from cat and human LES (20,
21) have demonstrated that the clasp has greater tension but
less cholinergic responsiveness than the sling. Furthermore, in
response to cholinergic stimulation, there are differences between the
LES and the EB in the predominant calcium source used for contraction
(3). Therefore, the present studies were performed to
1) assess differences of the active (response to
bethanechol) and passive properties of cat esophageal smooth muscle
isolated from proximal and distal regions of the EB and 2)
compare these differences in the EB with those seen in the clasp and
sling regions of the LES.
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MATERIALS AND METHODS |
Tissue removal.
The experimental protocol was approved by the University Health Network
Animal Care Committee. Adult cats of either sex weighing between 2.5 and 5.0 kg were anesthetized with ketamine hydrochloride (0.15 ml/kg
im; Bimeda-MTC, Cambridge, Ontario, Canada) and euthanized with
pentobarbital sodium (0.5 ml/kg iv; Bimeda-MTC). A midline incision was
made, and the chest was opened. A length of esophagus from 10 cm above
the LES to 4 cm below it was removed and immediately placed in Krebs
solution equilibrated with 5% CO2-95% O2 and
maintained at pH 7.4 ± 0.05.
Muscle strip preparation.
The specimen was freed of surrounding fascia and stretched to its in
situ length. The esophagus was then opened up along the greater
curvature, and the mucosa was removed by sharp dissection. The circular
and clasp fibers of the LES were readily visible (21).
Muscle strips measuring ~2 mm in width and 10 mm in length were
obtained from the circular smooth muscle esophagus and from the
circular (medial side) and sling fibers of the LES. Care was taken to
ensure that the orientation of the muscle fiber bundles ran parallel to
the long axis of the muscle strips. A silk thread was tied to each end,
and the strips were transferred to 25-ml organ baths containing Krebs
solution bubbled with 5% CO2-95% O2 at 37°C
and maintained at pH 7.4 ± 0.05. One end of the strip was fixed
to an electrode holder and the other end to an isometric force
transducer (model FT-03; Grass Instruments, Quincy, MA) coupled to a
chart recorder (model 79E; Grass Instruments). The force transducer was
supported on a rack-and-pinion clamp (Harvard Apparatus) that
facilitated accurate length adjustment of the muscle strips. Transmural
electrical field stimulation (EFS) was delivered by a Grass stimulator
(SP-9) through platinum wire electrodes placed on either side of the
tissue strips. EFS consisted of 0.5-ms square-wave pulses in a 5-s
train at 10 Hz and a strength of 50 V. Tissue strips were hung loosely
with no tension being applied to them in the organ baths for a 1-h
equilibration period before the studies commenced.
Length-tension relations.
To compare the length-tension relationships of muscle strips from
different regions, each strip was gently stretched to initial length
(L0), which was first determined with a micrometer as the length (in mm) at which a rapid stretch caused a small transient deflection of the recorder pen (~50 mg of tension). At
L0, any slack in the strip or silk ties was eliminated and
further stretch began to produce tension in response to stretch. The
muscle strip was then allowed to equilibrate at L0 for 30 min, during which time the strips could develop some tension, which was
called spontaneous tension. Muscle strips were then slowly stretched
sequentially and tested at increments of 25% of their L0
to a maximum of 250% L0 according to the protocols below.
Stretch-induced and total tension.
Initial stretch of 25% L0 resulted in the development of
tension in response to stretch, which was allowed to stabilize for 15 min, at which time the amplitude was recorded. Bethanechol (10
5 M) was then added to the chamber and was allowed to
act on the strips for 15 min. The tension at this time was defined as
the total tension. EFS was then carried out in the
bethanechol-contracted muscle strips to determine the maximal
relaxation response in these precontracted muscles. Bethanechol was
then washed out from the recording chamber with normal Krebs for 15 min, during which time baseline tension was reestablished at the given
level of stretch before the strips were stretched to the next length
and the protocol cycle was repeated.
To assess the passive mechanical properties of the tissue, a separate
set of length-tension experiments was carried out in a calcium-free
Krebs solution. The protocol was similar to that described above, the
only difference being the substitution of normal Krebs with
calcium-free Krebs solution.
A separate set of muscle strip experiments was carried out to
examine the neurogenic component of the spontaneous length-tension relations in the EB and LES. In these experiments, length-tension relationships of the muscle strips were carried out in the presence of
TTX (10
6 M). The parameter assessed was tension developed
in response to stretch.
At the end of all experiments, the strips were blotted on filter paper
and the wet weight was determined. Tension was then normalized to the
wet tissue weight and expressed in milliNewtons per milligram.
Composition of solutions.
The Krebs solution had the following composition (in mM): 115 NaCl, 4.6 KCl, 1.2 MgSO4, 1.2 NaH2PO4, 22 NaHCO3, 2 CaCl2, and 11 glucose. The
calcium-free medium contained (in mM): 115 NaCl, 4.6 KCl, 1.2 MgSO4, 1.2 NaH2PO4, 22 NaHCO3, 11 glucose, and 0.1 EGTA.
Drugs.
All drugs were obtained from Sigma Chemical (St. Louis, MO).
Bethanechol and TTX were prepared in double-distilled H2O
and added directly to the organ bath chamber from stock solution of 100× dilution.
Statistical analysis.
At L0, any tension generated during the 30-min
equilibration period in the absence of stretch or bethanechol was
defined as spontaneous tension. The parameters measured at each muscle
strip length were 1) tension developed in response to
stretch, which was called stretch tension, and 2) maximum
total tension, the total tension developed at each level of stretch
after bethanechol (10
5 M) challenge. Active tension at
each stretch length was calculated as maximum total tension in response
to bethanechol minus tension in response to stretch. Maximal relaxation
of tonically contracted muscle in response to EFS is expressed as a
percentage. Statistical comparisons were made with two-tailed paired
Student's t-test (using Instat Graph Pad software).
Data are presented as means ± SE, and n is the number
of cats. P < 0.05 was considered significant.
 |
RESULTS |
EB.
A dose-response curve was performed for bethanechol (3-100 µM)
on muscle strips from the EB prestretched to 130% L0. The
region of the EB 3 cm above the LES (EB3) consistently demonstrated a greater contractile response to bethanechol stimulation than the region
1 cm above the LES (EB1; Fig. 1;
n = 6). From this curve, 10
5 M
bethanechol was chosen because it resulted in near-maximal contraction
in all strips studied. Subsequent studies were then performed on strips
from both EB3 and EB1.

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Fig. 1.
Comparison of concentration-dependent increase in tension
in response to bethanechol in the esophageal body (EB). Note esophageal
circular smooth muscle from 3 cm above (EB3) the lower esophageal
sphincter (LES) demonstrated a greater contractile response to
bethanechol stimulation than at 1 cm above the LES (EB1).
*P < 0.05; n = 6.
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Muscle strips from all the regions examined showed an increase in
tension as their length was increased. Neither circular muscle from EB3
or EB1 produced any measurable spontaneous tension at L0
(Table 1). Circular muscle from EB3
developed significantly higher tension in response to stretch than
muscle from EB1 (Fig. 2A;
n = 9), and the first increase in tension occurred at
less stretch in EB3 (150% L0) than in EB1 (175%
L0). Moreover, the magnitude of the tension in response to
stretch was greater in EB3 than either sling or clasp muscle strips
(Table 1). To examine the role of neural innervation, separate
length-tension curves were determined in the presence of the sodium
channel blocker TTX. TTX (10
6 M) blocked EFS contractions
in all muscle strips studied. However, in the presence of TTX, there
were no significant changes in the length-tension relationships of EB3
and EB1 in response to stretch (Fig. 2B), the differences
between the two regions persisting.
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Table 1.
Summary of the effect of stretch and cholinergic stimulation on tension
development in esophageal body and lower esophageal sphincter
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Fig. 2.
Comparison of length-tension relationship in EB. A:
circular muscle from EB3 developed significantly higher stretch tension
than muscle from EB1 (*P < 0.05; n = 9). B: effect of TTX in the length-tension relationship of
the EB. In the presence of TTX (10 6 M), regional
differences in tension development in response to stretch persisted,
with circular muscle from EB3 developing significantly higher
stretch tension than muscle from EB1 (*P < 0.05;
n = 5).
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In response to cholinergic stimulation, regional differences within the
EB circular muscle were again observed in the length-tension experiments. Circular muscle from EB3 (34.47 ± 7.6 mN/mg)
produced significantly greater maximum total tension in response to
bethanechol (10
5 M) than the circular muscle from EB1
(18.18 ± 3.2 mN/mg; *P < 0.05 for EB3 vs. EB1;
Fig. 3). Although the maximum active
tension in response to bethanechol was similar at EB1 and EB3, the
maximum active tensions occurred at different lengths: 125%
L0 for EB3 and 150% L0 for EB1 (Table 1 and
Fig. 3). This latter difference is a reflection of the cholinergic
response in EB3 being most prominent between L0 and 150%
L0, whereas the response in EB1 was evident at all lengths
of stretch studied.

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Fig. 3.
Comparison of length-tension relationship and effect of bethanechol
on EB3 (A) and EB1 (B) muscle strips. In response
to bethanechol (10 5 M), circular muscle from EB3 produced
significantly greater total tension than the circular muscle from EB1
(*P < 0.05). Maximum active tension (maximum total
tension minus tension in response to stretch) of EB3 was greater at
100% L0 (L1) to 150% L0
(L1.5), where L0 is the initial length of the
strip. After 175% L0 (L1.75) EB1 had a greater
response to bethanechol (*P < 0.05; n = 9).
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Length-tension relationships were also determined in calcium-free Krebs
solution in separate sets of strips. Similar to experiments in normal
Krebs solution, EB3 developed significantly greater tension than EB1 in
response to stretch (Fig. 4A).
In calcium-free Krebs solution, bethanechol did not cause contraction,
nor was any change observed in the length-tension relationship (Fig.
4B).

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Fig. 4.
Comparison of length-tension relationship in the EB with
calcium-free Krebs solution. A: circular muscle from
EB3 developed significantly higher tension with stretch than muscle
from EB1. B: in calcium-free Krebs, bethanechol stimulation
did not effect the length-tension relationship in the EB.
(*P < 0.05, n = 5).
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Maximal relaxation induced by EFS was assessed after bethanechol
addition to the muscle strip chambers. Circular muscle from EB3 tends
to relax less in response to EFS than the muscle from EB1 (at 150%
L0, 34% vs. 63%; P < 0.05; Fig.
5A).

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Fig. 5.
Maximum relaxation to electrical field stimulation (EFS) of
bethanechol-induced contraction in EB (A) and LES
(B). A: circular muscle from EB3 tends to relax
less in response to EFS than the muscle from EB1 (at L1.5
34% relaxation vs. 63% relaxation; *P < 0.05;
n = 9). B: muscle strips from the sling and
clasp regions did not show a significant difference of relaxation in
response to EFS.
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LES.
Both sling and clasp muscles exhibited spontaneous tension development
at L0 (Table 1). Clasp muscle developed higher tension than
sling muscle with stretch up to 175% L0 (Fig.
6A; n = 9), but beyond this stretch the two muscles were similar (Table 1). As in
the control conditions, in the presence of TTX clasp muscle developed
higher stretch tension than sling muscle with stretch up to 175%
L0 (Fig. 6B; n = 5). Moreover,
neither spontaneous tension nor tension developed in response to
stretch was affected by addition of TTX to the baths (i.e., control
length-tension curve vs. TTX-treated length-tension curve) at any of
the lengths studied.

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Fig. 6.
Comparison of length-tension relationship in LES. A:
clasp muscle developed significantly higher spontaneous tension and
tension in response to stretch up to 175% L0
(*P < 0.05; n = 9). B: in
the presence of TTX (10 6 M), regional differences in
tension development in response to stretch persisted
(*P < 0.05; n = 5).
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In response to bethanechol (10
5 M), maximum total tension
generated by sling and clasp tissue at each stretch did not show any
significant difference (Fig. 7). However,
in response to bethanechol, the active tension (maximal total tension
minus tension in response to stretch at each length) was more than two
times greater in the sling muscle than the clasp muscle (Table 1 and
Fig. 7).

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Fig. 7.
Comparison of length-tension relationship and effect of bethanechol
on sling (A) and clasp (B) muscles. In response
to bethanechol (10 5 M), total tension generated by sling
and clasp did not show any difference. Maximum active tension (maximum
total tension minus tension in response to stretch) of sling was
greater than clasp muscle (*P < 0.05;
n = 9).
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Length-tension studies were also performed in calcium-free Krebs
solution (n = 5). Unlike the control studies, in which
spontaneous tension and tension in response to stretch were greater in
the clasp up to 175% L0, no significant differences in the
length-tension curves were observed between the sling and clasp muscle
strips under conditions of calcium-free Krebs (Fig.
8A). The two curves were
virtually identical and similar to the sling curve in normal Krebs
solution. Bethanechol stimulation produced no contraction of either
sling or clasp muscle at any stretch in the calcium-free Krebs
environment, the two length-tension curves again being virtually identical (Fig. 8B) and similar to the sling curve in normal
Krebs solution.

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Fig. 8.
Comparison of length-tension relationship in the LES with
calcium-free Krebs solution. A: in calcium-free Krebs, the
length-tension relationship of sling and clasp are identical.
B: bethanechol had no effect on LES length-tension curves
between sling and clasp strips in calcium-free Krebs (P > 0.05; n = 5).
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After bethanechol contraction in the LES, there was no significant
difference in relaxation induced by EFS between sling and clasp muscle
strips (Fig. 5B).
 |
DISCUSSION |
This study in the cat is the first study to examine length-tension
relationships in different regions of the circular smooth muscle of the
EB. Previous studies of length-tension relationships of the EB have
examined the distal 3-8 cm in the human (20, 29, 30)
and distal 0.5-2 cm in the cat (4, 21). However, these studies did not assess regional differences by differentiating between the proximal and distal portions of the smooth muscle esophagus
but rather pooled all of the results. Similarly, in the region of the
LES, only one study in the human assessed the sling and clasp fibers
separately (20), and studies in the cat used rings or
large segments of the LES that included both sling and clasp fibers
(4, 21). We found that circular smooth muscle from EB3
1) develops greater tension with stretch, and this
difference remains in calcium-free Krebs solution; 2) is
functionally more responsive to cholinergic excitation; and
3) is less responsive to inhibitory innervation than the
more distal (EB1) smooth muscle. We also found that in the isolated
regions of smooth muscle from the LES 1) clasp develops
greater spontaneous tension and tension with stretch than sling,
2) sling muscle demonstrates a much greater response to
cholinergic excitation, and 3) regional differences in
spontaneous and stretch-induced tension are abolished in calcium-free Krebs solution. The studies reported in this paper support the hypothesis that regional myogenic differences are present in the EB as
well as in the LES and are reflected in the length-tension characteristics and in the cholinergic sensitivity of the muscle. In
the EB, a study of only two sites does not determine whether these
regional differences represent a gradient along the esophagus or two or
more discrete regions. The previously demonstrated gradient in neural
responsiveness may favor the former interpretation.
EB.
Comparison of the length-tension relationships between EB1 and EB3 and
between the esophageal and LES clasp and sling regions demonstrates a number of differences that likely relate to the physical
properties of the contractile and noncontractile elements in the
different muscles and, potentially, to functional differences.
Tottrup et al. (30) have provided a proposed model for
esophageal smooth muscle based on the Hill-Maxwell model that includes the parallel elastic component (PEC), contractile element, and series
elastic component. In muscle strips of the human EB, there is little or
no spontaneous active tone (29) and the passive length-tension relationships are the same in normal Krebs and in
calcium-free medium. Our findings in the cat are similar, and furthermore the differences between EB1 and EB3 persisted in
calcium-free medium. That is, the passive length-tension relationship
in the EB is determined almost exclusively by the elements in the PEC that are independent of the active contractile machinery. Our findings
were not altered by neural blockade with TTX, indicating that the true
muscle response was assessed. Previous studies have also demonstrated
that tension was not affected by addition of TTX in either the LES or
EB (20, 29). However, those studies did not differentiate
between sling and clasp fibers in the LES or between different regions
along the EB. Nevertheless, in the human in vivo, there appears to be
an active component to resting tone of the EB, because amyl nitrate
inhalation can reduce the tone (11, 15). Presumably this
is neurally mediated.
The differences therefore in the length-tension relationship between
EB1 and EB3 must reside primarily in those elements unrelated to active
contraction. Differences in muscle fiber arrangement within the EB may
be present but have not as yet been assessed in esophageal muscle.
Connective tissue such as proteoglycans, glycoproteins, elastins, and
collagen are found in visceral smooth muscle and can affect the ability
of smooth muscle to develop tension with stretch. Collagen
concentration and the number and types of collagen cross-links
contribute to the passive components of the length-tension curves.
Previous studies examining collagen composition in the longitudinal and
circular layers of the EB and LES revealed no differences between
muscle types (29). More recently, connective tissue
composition in the lamina propria and submucosa of the opossum smooth
muscle esophagus found that the connective tissues of the two regions
are similar with regard to fiber orientation, but the lamina propria
contains relatively more collagen III (small fibril) and the submucosa
contains relatively more collagen I (large fibril) (14).
However, these studies did not compare collagen content along the EB at
different lengths or between clasp and sling fibers. It is possible
that there exists a greater amount of collagen and greater number of
collagen cross-links in EB3 than EB1 to account for the greater tension
in response to stretch.
In addition to the differences in the passive length-tension
relationships between EB1 and EB3, cholinergic stimulation with bethanechol demonstrated significant differences in the active contractile responses of the two regions. Both the maximum total and
active tension in response to bethanechol were greater in EB3 muscle.
The shape of the active component of the length-tension curve showed
increased tension with increasing length reaching a maximum, followed
by a decline with further stretch. This optimum tension is presumably
reached at a level of optimum overlap between the sliding filaments.
The maximum active tension occurred at less stretch in EB3 and rapidly
declined with increasing stretch, whereas that in EB1 not only occurred
at a greater length but persisted as stretch was increased. This is in
contrast to maximum total tension, which was consistently greater at
EB3 than EB1 at all lengths studied. These findings suggest that the
contractile proteins and/or the mechanisms that couple excitation to
contraction may be different in the two regions. Differences in these
proteins in phasic and tonic smooth muscles of the opossum EB and LES, respectively (28), and in the myosin phosphorylation of
these muscles in the cat esophagus (31) have been
demonstrated, but this type of analysis has not been applied to
regional differences in the EB.
Therefore, at EB3, the tension that developed with stretch beyond 175%
L0 was in large part determined by the passive components in the PEC, whereas at EB1, active contractile elements were
contributing to at least 225% L0. That is, distally the
PEC is more compliant and the active component is more responsive at
greater stretch, but the active component produces less overall tension
than that proximally at EB3. From a functional point of view, this
combination of differences could be seen as advantageous to distal
propulsion if a less compliant proximal region with more forceful
contraction led into a more compliant region where active muscle tone
could be more readily modulated to accommodate receptive relaxation. Of
interest in this regard, the contracted distal circular muscle from EB1
tended to relax more in response to EFS than the proximal muscle from
EB3. Although the relaxation was due to release of inhibitory
neurotransmitter from nerves, there is no definite objective evidence
that the inhibitory neural elements are different in number relative to
the smooth muscle content or in release of neurotransmitter along the
EB to explain an increasing functional effect distally along the
esophagus (16, 18, 19). Is it possible that, in
addition to myogenic differences in responsiveness to cholinergic
excitation, there are also regional myogenic differences in the
response to the inhibitory neurotransmitter nitric oxide? If so, this
type of difference may impact on the timing of the contraction and
therefore peristaltic velocity because delay of the contraction is
related to action of the inhibitory neurotransmitter (1, 6, 17,
32, 33).
The functional gradient in the nitregeric inhibitory influence
(increasing distally) and in the cholinergic excitatory influence (decreasing distally) along the esophagus appears to have importance in
regulating the timing of the peristaltic contraction, the former delaying the contraction, the latter tending to shorten the delay to
contraction onset. A more complete picture of how the balance between
the two influences could operate is given in recent reviews (7,
12). The regional differences shown in the present study of the
physical properties of the muscle in the presence and absence of
cholinergic stimulation were not designed to assess any potential effect on the timing of the contraction and its distal progression. The
findings are relevant to the amplitude of the contraction and the
compliance of the smooth muscle esophagus as noted above, as well as
the effect that these aspects may have on the passage of a bolus
distally. It is likely that differences in ion channels (24) and their role in regulating membrane potential as
well as the depolarizing and hyperpolarizing effects of the neural influences are more important in determining timing of the contraction, its velocity, and its direction. To what extent these latter
differences can affect timing by interacting with differences in
contraction characteristics, excitation-contraction coupling, and the
receptor-activated messenger systems are open to investigation.
LES.
Studies of the isolated LES clasp and sling muscles further defined the
length-tension relationships in these muscles and the differences in
their responsiveness to cholinergic stimulation, generally confirming
the previous findings in the isolated muscles in the human
(20) and in the more intact combined tissues in the cat
(21). The clasp muscle has much more spontaneous tone than
the sling but is much less responsive to cholinergic stimulation. Nevertheless, although the total tension at each stretch with cholinergic stimulation was slightly greater in the sling, this difference was not significant, suggesting that the spontaneous tone in
the clasp leaves limited extra room for further contraction.
The increase in tone in the clasp is evident with stretch up to 175%
L0, but at stretch of 200% L0 and greater, the
two muscles are similar, indicating that the noncontractile PEC
elements are at this stage dominant and are very similar in the two
muscles. The latter similarity is further evident in the length-tension relationships in calcium-free medium in which the active component is
now gone from the clasp muscle and the two curves are identical in the
presence or absence of bethanechol. We did not explore to what extent
the loss of clasp tone related to an intracellular or extracellular
source of calcium (3, 9). However, as with the differences
seen in the EB smooth muscle, further investigation is necessary to
establish the mechanisms responsible for the differences.
These additional findings have interesting functional implications in
vivo. Because the LES pressure profile shows a higher pressure in the
left lateral-posterior aspect in both the human (22, 25,
27) and the cat (21), this aspect being most sensitive to atropine, it is likely that the sling, in addition to the
clasp, is an integral and important physical (13) and physiological contributor to the LES. For this reason, Schneider et al.
(25) have raised the importance of regional LES
differences in patients with achalasia, and similar attention has been
paid to the two muscle regions and their potential role in the
pathogenesis of gastroesophageal reflux disease (27).
In conclusion, the different mechanical properties of the EB
smooth muscle from these two regions suggests that regional differences likely contribute to esophageal biomechanics and may play an important role in esophageal peristalsis. How these regional differences contribute to the peristaltic contraction (i.e., contractile
characteristics, including contraction amplitude, duration, and latency
to onset) have yet to be determined. Our studies indicate that the
differences in cholinergic responsiveness would impact at least on the
contractile properties such as contraction amplitude, but we did not
assess any role in determining latency of the contraction. Similarly, the LES regional differences are open to investigation in health and disease.
 |
ACKNOWLEDGEMENTS |
We thank Junzhi Ji for expert technical assistance.
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FOOTNOTES |
This work was supported by the Canadian Institute of Health Research.
Address for reprint requests and other correspondence: N. E. Diamant, Univ. Health Network (Western Division), 399 Bathurst St./Rm 12-419 McLaughlin Pavilion, Toronto, ON M5T 2S8, Canada.
The costs of publication of this
article were defrayed in part by the
payment of page charges. The article
must therefore be hereby marked
"advertisement"
in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Received 12 March 2001; accepted in final form 8 August 2001.
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