DEFORMATION OF THE BOWDITCH STAIRCASE IN CA2-OVERLOADED MAMMALIAN CARDIAC TISSUE - A CALCIUM PHENOMENON()

Concentrations of 1-4 mu mol l(-1) isoproterenol cause both in right v entricular papillary muscles and in enzymatically isolated myocytes of the guinea-pig a Ca2+ overload-induced state which is functionally ch aracterized by biphasic (multiphasic) twitches and biphasic (multiphas ic) intracellular calcium transients, respectively, during excitation- contraction coupling. This state was stabilized in the in vitro experi ments for some hours by a co-ordination of the interstimulus interval, the temperature of the superfusion fluid and the addition of calcium agonists. The functional stability is the precondition for the reprodu cibility of the experimental results particularly after the applicatio n of long-lasting stimulation programmes. Changes in the shape of biph asic contractions were compared with changes in the time course of bip hasic intracellular calcium transients using three manipulations of a different kind: (1) the interruption of the steady pacing rhythm, (2) the variation of the interstimulus interval, (3) the addition of ryano dine. It was shown that: (1) The BOWDITCH staircase in calcium overloa ded multicellular preparations is changed in that each individual comp onent of the twitch passes through its own staircase. A homologous beh aviour can be observed in the configuration of the phasic and tonic co mponent of biphasic intracellular calcium transients. (2) At different driving frequencies the relative proportion of the two components of a biphasic twitch corresponds to the time integrals of the two compone nts of biphasic intracellular calcium transients. (3) Ryanodine suppre sses both the first component of the biphasic twitch and the phasic co mponent of the biphasic intracellular calcium transient. The SR Ca2+-A TPase inhibitor thapsigargin increases the second component of the bip hasic calcium transient. This supports the hypothesis that the size of the tonic component is in part determined by intracellular calcium re uptake. The results of both kinds of experiments would be compatible w ith the assumption that in calcium overloaded mammalian cardiac cells calcium reaches the contractile system directly as well as via two int racellular stores ('extended two-Ca-store concept').