Calcium Requirements for Cardiac Myofibrillar Activation

Abstract

The amounts of calcium required to achieve various levels of myofibrillar activation in the dog heart were determined by measuring the dependence of myofibrillar calcium binding, myofibrillar adenosinetriphosphatase (ATPase), and isometric tension on free calcium concentration. Myofibrillar ATPase was half-maximal at 2.4 x 10 -6 M free calcium, and tension development was half-maximal at 2.0 x 10 -6 M free calcium. No simple relation between calcium binding and activation was found. For example, between 10 -8 M and 10 -6 M free calcium, an appreciable amount of calcium was bound to the myofibrils, but there was little activation of isometric tension. On the other hand, myofibrillar calcium binding was not saturated at levels of free calcium at which both tension and ATPase were maximal; therefore, it appears that only a portion of the total myofibrillar calcium binding sites control ATPase and tension. Using the information derived from the binding and activation studies together with our determination of the myofibrillar content of the dog heart, 47.5 mg myofibrillar protein/g wet heart, we calculated the calcium required to achieve various levels of myofibrillar activation in the intact ventricle. By this calculation method, development of half-maximal tension required 22.4 µmoles calcium/kg wet heart, and development of maximal isometric tension required 92.8 µmoles/kg wet heart.

Activation of thin-filament-regulated muscle by calcium ion: considerations based on nearest-neighbor lattice statistics.

“…1B. That this approximation is reasonable is indicated by the qualitative similarity between measurements ofthe Ca2+ activation ofATPase in isometric fibers (10,11) and those in myofibrils (17).…”

Permeability and structural studies of heart cell gap junctions under normal and altered ionic conditions

“…The intracellular Ca 2 + concentration range, which defines marginal permeability to full permeability of Chironomous salivary gland intercellular junctions, has been estimated by Rose et al (1977) as 5 x 10 -s (pCa=4.3) and 5 x 10 -~ (pCa=6.3), respectively. In heart tissue intracellular Ca 2 + rises and falls with each cycle of contraction and relaxation exactly in this range (Solaro et al, 1974). This observation raises the question of how heart cells prevent uncoupling on a beat-to-beat basis (see Weidmann, 1970).…”

“…The Ca z § concentration associated with partial activation varies from one species to the next. Most other estimates are higher than that of Fabiato and Fabiato, so the pCa 6.25-6.0 should be regarded as a lower limit (Solaro, Wise, Shiner & Briggs, 1974). This range of intracellular Ca 2 § concentrations is expected to lead to a block of cell coupling (Rose et al, 1977).…”

Measurement of rapidly exchangeable cellular calcium in the perfused beating rat heart.

“…Whether or not pool A is the sarcoplasmic reticulum, the evidence does support the participation of pool A in the beat-to-beat activation of contraction, for the following reasons. (i) The Ca2+ in pool A turns over rapidly, and its release to the cell could be triggered by the influx of extracellular Ca2+ and (ii) the size of pool A, especially when measured after isoproterenol treatment, is adequate to fully saturate the myofibrils with Ca2+ (25). Additional measurements are required to determine whether the effect of isoproterenol is due to actual enhancement in the steady-state size of pool A or to stimulation of the rate of turnover of pool A. Enhancement by isoproterenol ofinflux ofextracellular Ca2+ during depolarization has previously been reported (26).…”