Beta-adrenergic regulation of action potentials and automaticity in young and adult canine purkinje fibers

1994 ◽  
Vol 266 (6) ◽  
pp. H2310-H2319
Author(s):  
F. Charpentier ◽  
M. R. Rosen
Keyword(s):  
Cycle Length ◽  
Beta Agonist ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Purkinje Fibers ◽  
Transmembrane Potentials ◽  
Beta 2 ◽  
Electrophysiological Effects ◽  
Microelectrode Techniques ◽  
Diastolic Potential

To investigate developmental changes in the cellular electrophysiological effects of beta 1- and beta 2-adrenoceptor stimulation on canine Purkinje fibers (PF), we studied the effects of isoproterenol, a nonselective beta-agonist, and salbutamol, a preponderantly beta 2-agonist, alone or in presence of the selective beta 1-antagonist CGP-20712A or the beta 2-antagonist ICI-118551. Standard microelectrode techniques were used to study adult and neonatal (< 11 days) PF paced at a cycle length of 1 s or allowed to beat spontaneously. In paced adult PF, isoproterenol significantly increased the maximum diastolic potential and significantly decreased action potential duration at 60 and 90% of full repolarization (APD60 and APD90) in a concentration-dependent fashion. These effects were not observed in neonatal PF, which instead manifested a significant increase in phase 2 amplitude and APD30 that was not observed in adult PF. All these effects occurred as well with salbutamol but were less pronounced and required higher agonist concentrations. Isoproterenol decreased the automatic cycle length of adult fibers from 4,079 +/- 796 ms during control to 2,190 +/- 229 ms at 10(-5) M (P < 0.05) and from 1,535 +/- 105 to 1,249 +/- 90 ms in neonatal PF (P < 0.05). In both adults and neonates, > 90% of this effect was reached at a concentration of 10(-8) M. Salbutamol had the same effect but required higher concentrations. In both adults and neonates, the beta 2-antagonist ICI-118551 did not modify any of the effects of isoproterenol and salbutamol, whereas the beta 1-antagonist CGP-20712A significantly antagonized them. In conclusion, 1) the effects of beta-adrenergic stimulation on transmembrane potentials of canine PF change during development, both qualitatively (in paced PF) and quantitatively (in automatic PF) and 2) the responses seen are attributable to the activation of beta 1- and not beta 2-adrenoceptors.

Electrophysiological effects of alpha 2-adrenergic stimulation in canine cardiac Purkinje fibers

1995 ◽  
Vol 268 (5) ◽  
pp. H2024-H2035 ◽  
Author(s):  
R. A. Samson ◽  
J. J. Cai ◽  
E. F. Shibata ◽  
J. B. Martins ◽  
H. C. Lee
Keyword(s):  
Action Potential ◽  
Pertussis Toxin ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Purkinje Fibers ◽  
Cardiac Purkinje Fibers ◽  
Action Potential Prolongation ◽  
Delayed Afterdepolarizations ◽  
Baseline Values ◽  
Electrophysiological Effects

The effects of alpha 2-adrenergic stimulation on action potentials were measured in isolated canine Purkinje fibers. Action potential durations at 50 and 90% of repolarization (APD50 and APD90) were significantly prolonged by 0.25 microM l-norepinephrine + 0.5 microM dl-propranolol (NE+P) from baseline values of 166 +/- 7 and 249 +/- 9 (SE) ms (n = 7) to 174 +/- 7 and 265 +/- 9 ms, respectively (P < 0.05 for both). Selective alpha 2-blockade with 0.01 microM yohimbine (YO) reduced this prolongation by NE+P in APD50 and APD90 to 169 +/- 7 and 256 +/- 8 ms, respectively (P < 0.05 compared with NE+P). Additional selective alpha 1-blockade with 0.01 microM prazosin (PZ) completely blocked the effects of NE+P, returning APD50 and APD90 to 163 +/- 7 and 250 +/- 9 ms (not different from baseline). After incubation of isolated Purkinje fibers with pertussis toxin (1 microgram/ml), which reduced the availability of a 41-kDa membrane protein for ADP ribosylation by 70 +/- 7% (n = 4, P < 0.05), YO failed to reverse the prolongation in action potential durations brought on by NE+P, but the effects of PZ were intact. The effects of alpha 2-stimulation on beta-adrenergic-induced delayed afterdepolarizations (DADs) were studied by burst pacing of Purkinje fibers in Tyrode solution containing 7.5 mM Ca2+. The DADs induced in the presence of NE+PZ (beta- + alpha 2-stimulation) were significantly smaller in amplitude and required a shorter pacing cycle length to reach threshold than those induced in the presence of NE+PZ+YO (unopposed beta-adrenergic stimulation). Furthermore sustained triggered activity, seen in five of eight preparations under beta-stimulation, could no longer be elicited in the presence of beta- + alpha 2-stimulation. These results suggest that the postjunctional alpha 2-adrenergic receptors in canine Purkinje fibers are coupled to a pertussis toxin-sensitive G protein and that stimulation of these receptors leads to action potential prolongation and suppression of DADs induced by beta-adrenergic stimulation.

Acetylcholine lengthens action potentials of sheep cardiac Purkinje fibers

1980 ◽  
Vol 238 (2) ◽  
pp. H237-H243
Author(s):  
S. L. Lipsius ◽  
W. R. Gibbons
Keyword(s):  
Muscarinic Receptors ◽  
Action Potential Duration ◽  
Action Potentials ◽  
Purkinje Fibers ◽  
Diastolic Depolarization ◽  
Cardiac Purkinje Fibers ◽  
Rate Of Increase ◽  
Definite Sequence ◽  
Microelectrode Techniques ◽  
Diastolic Potential

The effect of acetylcholine (ACh) on the electrical activity of sheep cardiac Purkinje fibers was studied using standard microelectrode techniques. Most fibers showed a definite sequence of changes when exposed to ACh. Initially, action potential duration (APD) increased markedly. After about 20 s, the maximum diastolic potential (MDP) started to become more negative and, at the same time, the rate of increase in APD slowed. Once the MDP stabilized at a more negative level, the APD usually resumed its rapid increase. ACh also increased the slope of diastolic depolarization and made the plateau voltage more positive. APD was increased by ACh concentrations as low as 10(-7) M, and it increased with concentrations up to 10(-5) M (the highest concentration tested). ACh-induced increases in APD depended on the stimulation frequency; 2-min exposures to 10(-6) M ACh increased APD by 76.8 +/- 14.7% at 6 min-1 and 17.7 +/- 4.2% at 60 min-1. Atropine blocked all the effects of ACh. Hexamethonium did not prevent the ACh effects. It is concluded that ACh acts via muscarinic receptors. The changes in APD and MDP appear to be separate events, and it is difficult to see how the former effect may be explained by known actions of ACh.

Effect of acetylcholine on automaticity of canine Purkinje fibers

1976 ◽  
Vol 230 (1) ◽  
pp. 116-119 ◽  
Author(s):  
WW Tse ◽  
J Han ◽  
MS Yoon
Keyword(s):  
Inhibitory Effect ◽  
Appreciable Effect ◽  
Purkinje Fibers ◽  
Spontaneous Rate ◽  
Per Se ◽  
Microelectrode Techniques ◽  
Diastolic Potential

The effect of acetylcholine on automaticity of Purkinje fibers was studied in isolated canine false tendon preparations with conventional microelectrode techniques. Of 15 preparations with the control spontaneous rate of 12-60 beats/min, acetylcholine in a concentration of 0.5 mug/ml decreased the spontaneous rate by 20-87% in 13 preparations. This decrease in automaticity was due to a decrease in the slope of phase 4 depolarization and an increase in the maximum diastolic potential. The inhibitory effect of acetylcholine could be reversed by atropine in a concentration of 3 mug/ml in six preparations and prevented by pretreatment with atropine in another six preparations. Atropine per se did not have any appreciable effect on automaticity of Purkinje fibers. The results indicate that acetylcholine significantly suppresses automaticity of canine Purkinje fibers through its muscarinic action.

Beta-adrenergic effects on left ventricular filling: influence of aging and exercise training

1994 ◽  
Vol 77 (6) ◽  
pp. 2522-2529 ◽  
Author(s):  
J. R. Stratton ◽  
W. C. Levy ◽  
R. S. Schwartz ◽  
I. B. Abrass ◽  
M. D. Cerqueira
Keyword(s):  
Heart Rate ◽  
Endurance Training ◽  
Left Ventricular ◽  
Beta Agonist ◽  
Diastolic Filling ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
End Diastolic Volume ◽  
Before And After ◽  
Ventricular Filling

Reduced heart rate and contractile responses to beta-agonist stimulation characterize normal cardiac aging, but whether diastolic responses also decline with aging has not been determined in humans. Diastolic filling responses to isoproterenol were determined in 13 older (60–82 yr) and 11 young (24–32 yr) healthy men before and after endurance training. Filling rates were expressed in three ways: 1) normalized to end-diastolic volume per second, 2) normalized to stroke volume per second, and 3) as absolute milliliters of blood (ml.s-1.m-2). Peak early filling rates by all methods were reduced at rest and all isoproterenol doses with aging (all P < 0.0001 for old vs. young), whereas peak atrial filling rates were increased with aging. During isoproterenol, both peak early and peak atrial filling rates increased significantly (all P < 0.01); the increase in filling rates with isoproterenol was not different with aging (all NS for old vs. young x dose). Endurance training did not augment diastolic filling responses to isoproterenol. Although diastolic filling rates at rest are markedly altered by aging, diastolic filling responses to isoproterenol are not reduced with aging. Thus the age-associated declines in heart rate, ejection fraction, and cardiac output responses to beta-adrenergic stimulation with isoproterenol do not extend to diastolic filling responses.

The relationship between some beta-adrenergic mediated responses and plasma concentrations of adrenaline and cyclic AMP in man

1990 ◽  
Vol 122 (1) ◽  
pp. 115-120 ◽  
Author(s):  
E. K. Philipsen ◽  
J. Myhre ◽  
S. Larsen ◽  
M. Damkjær Nielsen ◽  
J. J. Holst ◽  
...  
Keyword(s):  
Cyclic Amp ◽  
Plasma Concentrations ◽  
Beta Agonist ◽  
Beta Blockade ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Plasma Adrenaline ◽  
Beta Adrenoceptor ◽  
Adrenaline Infusion ◽  
The Relationship

Abstract To test the hypothesis that increments in plasma cyclic AMP during beta-adrenergic stimulation reflect integrated second messenger function of the tissues activated by the angonist, graded adrenaline infusion resulting in plasma adrenaline concentrations within the physiological range was performed in 8 healthy subjects with and without concomitant beta-adrenoceptor blockade by iv propranolol. A significant correlation was found between increments in plasma adrenaline and plasma cyclic AMP in the experiments without beta-blockade; during concomitant beta-blockade the increase in plasma cyclic AMP concentrations at low adrenaline infusion rates was prevented, whereas a small increase in cyclic AMP was found at high adrenaline infusion rates, probably owing to incomplete beta-receptor blockade. Likewise, the adrenaline-induced increments in blood substrates (glucose, lactate, glycerol and betahydroxy butyric acid) were significantly reduced but not completely prevented by beta-blockade. We conclude that an altered relationship between beta-agonist concentrations and plasma cyclic AMP may provide evidence for the existence of differences in beta-adrenergic sensitivity in man.

Depressed [Ca2+]i responses to isoproterenol and cAMP in isolated cardiomyocytes from experimental diabetic rats

1994 ◽  
Vol 266 (6) ◽  
pp. H2334-H2342 ◽  
Author(s):  
Z. Yu ◽  
G. A. Quamme ◽  
J. H. McNeill
Keyword(s):  
Diabetic Rats ◽  
Beta Agonist ◽  
Diabetic Rat ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Protein Activity ◽  
Concentration Dependent Manner ◽  
Beta Adrenergic ◽  
Beta Adrenoceptor ◽  
Diabetic Myocardium

Experimentally, diabetic rat hearts are characterized by diminished responses to beta-adrenergic stimulation. Among the aberrant responses are diminished beta-adrenoceptor number and depressed contractile protein activity. In this study, intracellular Ca2+ concentration ([Ca2+]i) was determined by microfluorescence in response to beta-adrenergic stimulation to understand the basis for the changes in the beta-adrenergic pathway in diabetic myocardium. In quiescent myocytes, isoproterenol caused a decrease in [Ca2+]i, which was blocked by timolol and thapsigargin. This suggests that the beta-agonist-induced [Ca2+]i changes are mediated, in part, by sarcoplasmic reticulum Ca-adenosinetriphosphatase. Diabetic myocytes showed a blunted response to isoproterenol, which was reversed by insulin treatment. In electrically stimulated myocytes, isoproterenol and 8-bromo-adenosine 3',5'-cyclic monophosphate (cAMP) increased [Ca2+]i and contraction in a concentration-dependent manner. Electrically stimulated diabetic myocytes demonstrated a depressed maximum [Ca2+]i response to isoproterenol and 8-bromo-cAMP without a change in sensitivity. These data suggest that in addition to alterations in beta-adrenoceptor function there are postreceptor defects in diabetic myocardium that may impair the regulation of [Ca2+]i in diabetic myocardium.

Peptide YY antagonizes beta-adrenergic-stimulated release of insulin in dogs

1988 ◽  
Vol 254 (4) ◽  
pp. E513-E517
Author(s):  
G. H. Greeley ◽  
F. Lluis ◽  
G. Gomez ◽  
J. Ishizuka ◽  
B. Holland ◽  
...  
Keyword(s):  
Insulin Release ◽  
Inhibitory Action ◽  
Peptide Yy ◽  
Beta Agonist ◽  
Dependent Manner ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Glucose Levels ◽  
Central Nervous Systems ◽  
Colon And Rectum

Peptide YY (PYY) and neuropeptide Y (NPY) are peptides of 36 amino acids that share structural homologies with pancreatic polypeptide (PP). PP is predominantly found in the endocrine pancreas. PPY is primarily found in mucosal endocrine cells of the distal ileum, colon, and rectum, whereas NPY is found in both the peripheral and central nervous systems. Previous studies indicate that these peptides can interact with the autonomic nervous system. The objective of the present experiments was to study the effect of PYY on neurally stimulated insulin release [i.e., in response to 2-deoxy-D-glucose (2-DG), a nonmetabolizable glucose analogue] in conscious dogs. Intravenous administration of PYY (100, 200, and 400 pmol.kg-1.h-1) reduced 2-DG-stimulated insulin release in a dose-dependent manner (P less than 0.05) without affecting plasma glucose levels. Administration of NPY (800 pmol.kg-1.h-1), but not PP (400 pmol.kg-1.h-1), reduced 2-DG-stimulated release of insulin (P less than 0.05). The inhibitory action of PYY on 2-DG-stimulated insulin release persisted in the presence of atropine or phentolamine treatment; however, hexamethonium alone or phentolamine plus propranolol treatment blocked the inhibitory action of PYY. Release of insulin stimulated by the beta-agonist isoproterenol was also inhibited by PYY (P less than 0.05). These results indicate that PYY can inhibit autonomic neurotransmission by a mechanism that may involve ganglionic or postganglionic inhibition of beta-adrenergic stimulation. Our findings suggest a role for PYY and NPY in the autonomic regulation of insulin release.

Effect of oxygen tension on catecholamine-induced formation of cAMP and on swelling of carp red blood cells

1990 ◽  
Vol 259 (5) ◽  
pp. C723-C726 ◽  
Author(s):  
A. Salama ◽  
M. Nikinmaa
Keyword(s):  
Red Blood Cells ◽  
Cell Volume ◽  
Oxygen Tension ◽  
Blood Cells ◽  
Beta Agonist ◽  
Cell Swelling ◽  
Adrenergic Stimulation ◽  
Maximal Increase ◽  
Beta Adrenergic ◽  
Hypoxic Conditions

We studied the effects of beta-adrenergic stimulation on the formation of adenosine 3',5'-cyclic monophosphate (cAMP) and on the cell volume in carp red blood cells in normoxia (PO2 = 150 mmHg) and hypoxia (PO2 = 8 mmHg). Accumulation of cAMP was the prerequisite for adrenergic cell swelling. Cell swelling was induced by beta-agonists, forskolin, and 8-bromo-cAMP. The amount of cAMP required for adrenergic swelling was minimal; swelling was observed at cAMP concentrations greater than 100 nM. Maximal increase in cell volume was observed at 200 nM cAMP. These values were independent of both the oxygen tension and the beta-agonist used. Norepinephrine caused the largest accumulation of cAMP, followed by isoproterenol and epinephrine. At hypoxic conditions, the cAMP concentrations obtained after stimulation with the natural catecholamines norepinephrine and epinephrine were greater than at normoxic conditions. The catecholamines caused appreciable cell swelling at lower concentrations in hypoxia than in normoxia. Thus the number of beta-adrenergic receptors, and their inherent ligand affinities, may be higher in hypoxic than in normoxic carp red blood cells. Oxygen tension had a pronounced effect on the magnitude of the adrenergic swelling. The maximal increase in cell volume was 5-7% in hypoxia, whereas in normoxia it was only approximately 2%. This was not due to differences in cAMP formation, but possibly to a greater activity of the Na(+)-H+ exchanger in hypoxic than in normoxic conditions.

Beta-adrenergic stimulation of brown adipocyte proliferation

1988 ◽  
Vol 254 (1) ◽  
pp. C175-C182 ◽  
Author(s):  
A. Geloen ◽  
A. J. Collet ◽  
G. Guay ◽  
L. J. Bukowiecki
Keyword(s):  
Endothelial Cells ◽  
Mitotic Activity ◽  
Cold Exposure ◽  
Tritiated Thymidine ◽  
Precursor Cells ◽  
Beta Agonist ◽  
Brown Adipocyte ◽  
Adrenergic Stimulation ◽  
Beta Adrenergic ◽  
Brown Adipose

The mechanisms of brown adipose tissue (BAT) growth were studied by quantitative photonic radioautography using tritiated thymidine to follow mitotic activity. To identify the nature of the adrenergic pathways mediating brown adipocyte proliferation and differentiation, the effects of cold exposure (4 days at 4 degrees C) on BAT growth were compared with those induced by treating rats at 25 degrees C with norepinephrine (a mixed agonist), isoproterenol (a beta-agonist), and phenylephrine (an alpha-agonist). The drugs were continuously administrated via osmotic minipumps (0.375 mumol/h during 4 days) implanted subcutaneously. Cold exposure markedly enhanced the mitotic activity in brown adipocyte precursor cells (interstitial cells and preadipocytes) and endothelial cells forming the numerous capillaries. Norepinephrine mimicked the effects of cold exposure, not only on the mitotic activity, but also on the distribution of the labeling among the various cellular types. Isoproterenol entirely reproduced the effects of norepinephrine both on the labeling index and on the cellular type labeling frequency. In contrast, phenylephrine did not stimulate cell division. These results demonstrate that norepinephrine triggers a coordinated proliferation of brown adipocytes and endothelial cells in warm-exposed rats that is similar to that observed after cold exposure. They also suggest that cold exposure stimulates BAT growth by increasing the release of norepinephrine from sympathetic nerves and that the neurohormone activates mitoses in BAT precursor cells via beta-adrenergic pathways.

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