Threephasic contractions in mammalian myocardium. Isolation and identification of a late component. Implications for...

More than 100 years after Bowditch's discovery of the "Treppe" phenomenon the mechanism of the striking rate and rhythm dependence of cardiac contraction is not unequivocally established. Beside sophisticated techniques biphasic contractions seemed to be a promising approach. There was soon a general agreement that the first component of biphasic contractions is activated by Ca released from the sarcoplasmic reticulum. About the second component prevails confusion: It does not directly reflect the Ca current, but is somehow related to that. In addition, involvement of Na-Ca exchange is supposed. We produced threephasic contractions by the use of isoproterenol (0.5-.4 microM) in guinea pig papillary muscle. Either by the application of ryanodine (1 microM) or after long periods of rest a ryanodine resistant late component of contraction could be isolated. On reducing the transmembrane Na gradient either by reducing [Na]o or by experimental manoeuvres expected to increase [Na]i. (.5 mM [K]o; 2-8 microM ouabain) this component was found to be increased. The evidence suggests that this component is substantially activated by Ca entering the cell via the sarcolemmal Na-Ca exchange. The ryanodine sensitive first component of threephasic contractions was found to be sensitive to caffeine, isoproterenol and changes in stimulation as well. These findings support the view that it may be generated by Ca induced Ca release from the sarcoplasmic reticulum. The pharmacological properties of the second and third ryanodine sensitive component and its dependence on the stimulation pattern were similar to those of the aftercontraction. They were found to be sensitive to procaine, verapamil, Mg, Ni and isoproterenol.(ABSTRACT TRUNCATED AT 250 WORDS)