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Extracellular Ca 2+ is obligatory for ouabain‐induced potentiation of cardiac basal energy expenditure
Author(s) -
Guild SJ,
Ward ML,
Cooper PJ,
Hanley PJ,
Loiselle DS
Publication year - 2003
Publication title -
clinical and experimental pharmacology and physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.752
H-Index - 103
eISSN - 1440-1681
pISSN - 0305-1870
DOI - 10.1046/j.1440-1681.2003.03800.x
Subject(s) - ouabain , diastole , chemistry , long term potentiation , intracellular , extracellular , perfusion , biophysics , ventricle , medicine , calcium , oxygen , cardiac glycoside , endocrinology , biochemistry , biology , sodium , receptor , organic chemistry , blood pressure
Summary 1. The method of action of cardiac glycosides is commonly explained by the ‘pump‐inhibition hypothesis’: inhibition of the Na + /K + ‐ATPase allows [Na + ] i to rise, eventually reversing Na + /Ca 2+ exchange. The resulting influx of Ca 2+ o increases [Ca 2+ ] i , thereby activating intracellular Ca 2+ ‐dependent ATPases and, hence, energy demand. This sequence has been presumed to occur during diastole as well as systole. However, it has been reported that dihydro‐ouabain‐induced potentiation of heat production by quiescent ventricular trabeculae persists in the absence of Ca 2+ o . This implies that the pump‐inhibition hypothesis is inapplicable during diastole. 2. We tested this implication by: (i) measuring the rate of oxygen consumption (V o 2 ) of arrested guinea‐pig whole‐hearts; (ii) measuring[Ca 2+ ] i in quiescent ventricular trabeculae; and (iii) mathematical modelling using software (Oxsoft Heart, Oxford Software, Oxford, UK) based on DiFrancesco‐Noble formalism. 3. Upon induction of arrest, whole heart V o 2 fell to one‐quarter of its ‘beating’ value. Subsequent perfusion with ouabain (20 µmol/L), in the presence of Ca 2+ o , increased V o 2 fourfold. This increase was prevented by withholding Ca 2+ o . Comparable results were obtained in quiescent trabeculae: ouabain increased [Ca 2+ ] i only if Ca 2+ o was present. Mathematical modelling readily simulated these experimental results. 4. We conclude that influx of Ca 2+ o is mandatory for potentiation of cardiac basal metabolism by cardiac glycosides.