The influence of metabolic inhibitors upon the transmembrane slow inward current in the mammalian ventricular myocardium

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Abstract
The effect of metabolic alterations of isolated trabeculae and papillary muscles of cats upon the transmembrane slow inward current was studied in voltage clamp experiments using the double sucrose gap technique. The slow inward current which is mainly carried by Ca ions was separated from the fast Na current by applying the conditioning clamp technique. After inhibition of the oxidative phosphorylation of the myocardial cell caused by cyanide (100 mg/l), the transmembrane slow inward current decreased by 25% on average within 25 min. The same diminution appeared after poisoning with 2.4 dinitrophenol (40 mg/l) which amounted to 46% on an average. In both cases the extrapolated reversal potential of the slow inward current was shifted to less positive values. The reduction of the slow inward current seems to reflect a diminished Ca driving force due to a metabolically evoked increase in intracellular free Ca. But these metabolic inhibitors might exert some direct effects upon the membrane since after the treatment with cyanide and 2.4 dinitrophenol, respectively, a slight delay of current inactivation could be observed. Nevertheless, the kinetics of the recovery from inactivation remained unaffected. Metabolic poisoning abolished the normal response of the slow inward current to an increase of the extracellular Ca concentration or to the addition of Sr ions. Excess Ca failed to augment the current, and in some cases even a slight diminution occurred. If at all 5.5 mM Sr caused an increase by not more than 20%. These unusual reactions may also result from a reduced driving force for Ca or Sr, respectively. Catecholamines still exerted their promoting effects upon the slow inward current after poisoning with cyanide or 2.4 dinitrophenol. The addition of 5 mg/l isoproterenol not only neutralized the effects of these metabolic inhibitors but caused an increase of the slow inward current even surpassing the initial control values.