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The electrical response of pulmonary artery muscle to acetylcholine, histamine and serotonin
Life Sciences Vol. 4, pp . 1025-1029, 1985 . Pergamon Press Ltd. Great Britain.
Printed in
THE ELECTRICAL RESPONSE OF PULMONARY ARTERY MUSCLE TO ACETYLCHOLINE, HISTAMINE AND SEROTONIN Che Su* and John A . Bevan Department of Pharmacology, UCLA Center for Health Sciences Loe Angeles, California 90024 (Received 4 March 1985) Although many types of smooth muscle have been shown to display electrical activities associated with contraction, others have been found to be relatively quiescent . pulmonary artery is an example of the latter .
The isolated rabbit The muscle cells
in this blood vessel showed no change in membrane potential during contraction induced either by stimulation of the sympathetic nerve supply or the application of 1-norepinephrine .
How-
ever, a contraction hought about by an increase in the concentration of extracellular potassium ions was invariably associated with a smooth sustained depolarization (1) . As the contractile response of this artery to norepinephrine appears to be basically different from those to acetylcholine, histamine and serotonin, in view of its unique susceptibility to temperature fall (2), the present electrophysiological study was undertaken to determine the effect of these humoral agents on the muscle membrane potential . Methods As described previously (1), the main pulmonary artery was isolated in the form of a ring 7-10 mm wide, and mounted in Krebs bicarbonate bath at 38°C . *Present address :
The isometric contraction of the
Riker Laboratories, Northridge, California . 1025
PULMONARY ARTERY MUSCLE
1028
Vol. 4, No. 10
arterial muscle was recorded using a strain gauge, and the changes in muscle membrane potential by an intracellular glass microelectrode of 20-50 megohm resistance .
Bath concentrations of
acetylcholine chloride, histamine dihydrochloride and serotonin creative-sulfate are expressed in terms of their salts . Results Since the results with histamine, serotonin and acetylcholine are similar, they will not be described separately .
Following
the addition of submaximal doses of histamine, the tranamembrane potential of an impâled muscle cell decreased steadily, from its mean resting level of 51 .5 mV (FIG . 1) .
0 50
[
MV
4
~G o T RIST.
FIG . 1 Effect of histamine (1 x 10' 5 ) on membrane potential and muscle tension of rabbit pulmonary artery . Time scale 1 sec . The paper speed was reduced towards the end of the trace . The depolarization attained a plateau in approximately 1 min, which preceded by several minutes the development of maximum muscle tension .
Action potentials were absent, even after the
Vol. 4, No. 10
PULMONARY ARTERY MUSCLE
onset of contraction .
The results of a prolonged experiment with
1027
serotonin are reconstructed and shown in FIG . 2 .
10 min
FIG . 2 Reconstruction of effect of serotonin (1 x 10'5 ) on membrane potential and muscle tension of rabbit pulmonary artery . Each dot indicates the membrane potential recorded from a muscle cell . Groups of no less than 6 muscle cells were impaled in the absence and presence of this agonist, and the mean potentials of the two groups compared .
Serotonin produced a depolarization
which persisted for more than 30 min .
In -view of the variation
in membrane potential, it was uncertain whether any small potential change concomitant with fading of the contraction occured . The actions of acetylcholine was quaïitativaly similar to those described above .
Thus the responses of pulmonary artery muscle
to histamine, serotonin and acetylcholine shared common features, namely, tonic contraction accompanied by, but not synchronous with, a smooth membrane depolarization .
In these respects these drugs
resemble potassium ion increase and contrast with norepinephrine .
1028
PULMONARY ARTERY MUSCLE
Vol. 4, No. 10
TABLE 1 Depolarization and Contraction of the Rabbit Pulmonary Artery Muscle by Various Stimulants . No . Depolarization Contraction Stimulant of Expts . mean ± S .E . mean t S .E . g KC1 -4 x normal conen 6 21 .4 t 1 .5 6 .5 t 1 .0 Serotonin
10 -5
Histamine
10 -5
Acetylcholine
10
-5
4
12 .3 t 1 .7
6 .6 t 1 .1
3
11 .7 ± 0 .8
4 .2 t 2 .0
4
9 .0 ± 2 .2
2 .7 ± p .4
Discussion In TABLE 1, the maximum levels of depolarization and peak increase in muscle tension elicited by the above agents and by potassium are summarised .
In each experiment, the depolarization
was significant at 5$ level .
It will be noted that the depolari-
zation in response to all the three agents was of similar magnitude, despite the fact that the magnituc:e of contraction differed markedly .
These results and the different time courses of depol-
arization and contraction suggest that there is no strict relationship between the electrical and mechanical activities in this muscle .
It is relevant that, according to our preliminary unpub-
lished observations, extensive depolarization of pulmonary arterial muscle did not abolish its contraction by these three humoral substances and by norepinephrine .
It appears possible that in
vascular muscle an electrical event may be associated with the contractile process induced by certain stimulants, but that such an event is not indispensable . In summary, the transmembrane potential of the smooth muscle of rabbit pulmonary artery was investigated with regard to druginduced contraction .
The muscle underwent smooth sustained mem
brane depolarization when it contracted in response to acetylcholine, histamine and serotonin, as well as potassium.
This
Vol. 4, No. 10
PULMONARY ARTERY MUSCLE
1029
depolarization showed a very different time course from contraction .
These results contrast with our previous finding that the
same muscle remained electrically quiescent during contraction brought about by norepinephrine and sympathetic nerve stimulation, and provide additional evidence for the unique nature of the vasoconstrictor action of norepinephrine . References 1.
C . Su, J .A . Bevan and R .C . Ursillo, Circulation Res . 15, 20 (1964) .
2.
C . Su and K .H . Ginzel, Pharmacologist 6, 193 (1964) .
(Supported by Grant G-18973 from the National Science Foundation)
Printed in
THE ELECTRICAL RESPONSE OF PULMONARY ARTERY MUSCLE TO ACETYLCHOLINE, HISTAMINE AND SEROTONIN Che Su* and John A . Bevan Department of Pharmacology, UCLA Center for Health Sciences Loe Angeles, California 90024 (Received 4 March 1985) Although many types of smooth muscle have been shown to display electrical activities associated with contraction, others have been found to be relatively quiescent . pulmonary artery is an example of the latter .
The isolated rabbit The muscle cells
in this blood vessel showed no change in membrane potential during contraction induced either by stimulation of the sympathetic nerve supply or the application of 1-norepinephrine .
How-
ever, a contraction hought about by an increase in the concentration of extracellular potassium ions was invariably associated with a smooth sustained depolarization (1) . As the contractile response of this artery to norepinephrine appears to be basically different from those to acetylcholine, histamine and serotonin, in view of its unique susceptibility to temperature fall (2), the present electrophysiological study was undertaken to determine the effect of these humoral agents on the muscle membrane potential . Methods As described previously (1), the main pulmonary artery was isolated in the form of a ring 7-10 mm wide, and mounted in Krebs bicarbonate bath at 38°C . *Present address :
The isometric contraction of the
Riker Laboratories, Northridge, California . 1025
PULMONARY ARTERY MUSCLE
1028
Vol. 4, No. 10
arterial muscle was recorded using a strain gauge, and the changes in muscle membrane potential by an intracellular glass microelectrode of 20-50 megohm resistance .
Bath concentrations of
acetylcholine chloride, histamine dihydrochloride and serotonin creative-sulfate are expressed in terms of their salts . Results Since the results with histamine, serotonin and acetylcholine are similar, they will not be described separately .
Following
the addition of submaximal doses of histamine, the tranamembrane potential of an impâled muscle cell decreased steadily, from its mean resting level of 51 .5 mV (FIG . 1) .
0 50
[
MV
4
~G o T RIST.
FIG . 1 Effect of histamine (1 x 10' 5 ) on membrane potential and muscle tension of rabbit pulmonary artery . Time scale 1 sec . The paper speed was reduced towards the end of the trace . The depolarization attained a plateau in approximately 1 min, which preceded by several minutes the development of maximum muscle tension .
Action potentials were absent, even after the
Vol. 4, No. 10
PULMONARY ARTERY MUSCLE
onset of contraction .
The results of a prolonged experiment with
1027
serotonin are reconstructed and shown in FIG . 2 .
10 min
FIG . 2 Reconstruction of effect of serotonin (1 x 10'5 ) on membrane potential and muscle tension of rabbit pulmonary artery . Each dot indicates the membrane potential recorded from a muscle cell . Groups of no less than 6 muscle cells were impaled in the absence and presence of this agonist, and the mean potentials of the two groups compared .
Serotonin produced a depolarization
which persisted for more than 30 min .
In -view of the variation
in membrane potential, it was uncertain whether any small potential change concomitant with fading of the contraction occured . The actions of acetylcholine was quaïitativaly similar to those described above .
Thus the responses of pulmonary artery muscle
to histamine, serotonin and acetylcholine shared common features, namely, tonic contraction accompanied by, but not synchronous with, a smooth membrane depolarization .
In these respects these drugs
resemble potassium ion increase and contrast with norepinephrine .
1028
PULMONARY ARTERY MUSCLE
Vol. 4, No. 10
TABLE 1 Depolarization and Contraction of the Rabbit Pulmonary Artery Muscle by Various Stimulants . No . Depolarization Contraction Stimulant of Expts . mean ± S .E . mean t S .E . g KC1 -4 x normal conen 6 21 .4 t 1 .5 6 .5 t 1 .0 Serotonin
10 -5
Histamine
10 -5
Acetylcholine
10
-5
4
12 .3 t 1 .7
6 .6 t 1 .1
3
11 .7 ± 0 .8
4 .2 t 2 .0
4
9 .0 ± 2 .2
2 .7 ± p .4
Discussion In TABLE 1, the maximum levels of depolarization and peak increase in muscle tension elicited by the above agents and by potassium are summarised .
In each experiment, the depolarization
was significant at 5$ level .
It will be noted that the depolari-
zation in response to all the three agents was of similar magnitude, despite the fact that the magnituc:e of contraction differed markedly .
These results and the different time courses of depol-
arization and contraction suggest that there is no strict relationship between the electrical and mechanical activities in this muscle .
It is relevant that, according to our preliminary unpub-
lished observations, extensive depolarization of pulmonary arterial muscle did not abolish its contraction by these three humoral substances and by norepinephrine .
It appears possible that in
vascular muscle an electrical event may be associated with the contractile process induced by certain stimulants, but that such an event is not indispensable . In summary, the transmembrane potential of the smooth muscle of rabbit pulmonary artery was investigated with regard to druginduced contraction .
The muscle underwent smooth sustained mem
brane depolarization when it contracted in response to acetylcholine, histamine and serotonin, as well as potassium.
This
Vol. 4, No. 10
PULMONARY ARTERY MUSCLE
1029
depolarization showed a very different time course from contraction .
These results contrast with our previous finding that the
same muscle remained electrically quiescent during contraction brought about by norepinephrine and sympathetic nerve stimulation, and provide additional evidence for the unique nature of the vasoconstrictor action of norepinephrine . References 1.
C . Su, J .A . Bevan and R .C . Ursillo, Circulation Res . 15, 20 (1964) .
2.
C . Su and K .H . Ginzel, Pharmacologist 6, 193 (1964) .
(Supported by Grant G-18973 from the National Science Foundation)