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PMID: 4376168 Published · ppublish English Journal Article

Localization of beta adrenergic receptors, and effects of noradrenaline and cyclic nucleotides on action potentials, ionic currents and tension in mammalian cardiac muscle.

The Journal of physiology ·Vol. 242 ·No. 2 ·1974-10-00 ·Pages 429-51

Reuter H

Abstract

1. Isoprenaline and noradrenaline were applied iontophoretically to cardiac Purkinje fibres. Intracellular application of the drugs had no effect, while extracellular application of the same amounts of charge caused acceleration of pace-maker activity and a shift of the plateau level of the action potential. These results indicate that beta-adrenergic receptors are located at the outside of the cardiac cell membrane.2. A systematic comparison of the effects of cyclic AMP derivatives and noradrenaline on action potentials and isometric tension of ventricular myocardial preparations showed that the nucleotides and the catecholamine increase the plateau height and the duration of the action potential and also increase tension. However, there are quantitative differences in the action of these drugs.3. Cyclic AMP derivatives and noradrenaline increase the slow inward current, I(Ca), in ventricular myocardial preparations. Voltage clamp analysis of I(Ca) showed that the kinetic parameters of this membrane current are not affected by these drugs. However, the membrane conductance to Ca ions is greatly increased by noradrenaline and to a smaller extent by dibutyryl cyclic AMP.4. Concentration-response relations of the membrane effects of noradrenaline on plateau height of the action potential and on I(Ca) could be fitted by the same theoretical log concentration-response curve. The Hill plot of this concentration-response curve had a slope of 2. The half maximal response occurred at 5 x 10(-7)M.5. The results are compared with other membrane effects of catecholamines and cyclic nucleotides in cardiac muscle. The effects on I(Ca) are related to the positive inotropic effect of the drugs.

MeSH Terms
Action Potentials/drug effects Animals Bucladesine/pharmacology Cats Cattle Cyclic AMP/pharmacology Dose-Response Relationship, Drug Electric Conductivity Heart/drug effects Heart Conduction System/drug effects Heart Rate/drug effects In Vitro Techniques Iontophoresis Isoproterenol/pharmacology Membrane Potentials/drug effects Norepinephrine/administration & dosage,pharmacology Purkinje Fibers/drug effects Receptors, Adrenergic Stimulation, Chemical Tetrodotoxin/pharmacology Time Factors
Chemicals
Receptors, Adrenergic Tetrodotoxin Bucladesine Cyclic AMP Isoproterenol Norepinephrine
Authors & Affiliations
1 authors, click to expand affiliations / ORCID
Reuter H
References (50)
50 references, click to expand
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Article Info
Journal
The Journal of physiology
Abbr.
J Physiol
ISSN
0022-3751
DOI
10.1113/jphysiol.1974.sp010716
Published
1974-10-00
Pages
429-51
Language
English
Region
England
NLM ID
0266262
PMCID
PMC1330676
Subset
IM
External Links
PubMed source DOI: 10.1113/jphysiol.1974.sp010716 PMC Full Text View journal details
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