Myocardial calcium compartmentation and contractile control

Under the condition of rapid perfusion, the time course of contractile response of single ventricular cells to extracellular calcium (Ca) depletion and repletion identifies „fast” and „slow” cellular Ca pools. ⁴⁵Ca exchange was studied in these cells under the same conditions of on-line rapid perfusion. Four kinetically-defined compartments were distinguished: (1) A „rapid” compartment containing 2.6mmoles Ca/kg dry wt of lanthanum (La) displaceable Ca, t½ < 1 sec.; (2) An „intermediate” compartments) containing 2.1 mmoles, t½ = 3 and 19 sec. Caffeine displaced significant amounts of Ca from this compartment whereas La displaced none; (3) A „slow” compartment containing 1.6 mmoles, t½ = 3.6 min. Addition of inorganic phosphate to the perfusate adds significant amounts of Ca to this compartment; (4) An „inexchangeable” compartment, containing 1.2 mmoles. The „rapid” compartment’s flux is > 300 µmoles Ca/kg wet wt/sec. Its exchange rate indicates that it is the kinetic counterpart of the functionally-defined „fast” pool. Its subcellular locus is undefined. The „intermediate” compartment is best correlated with the „slow” pool and represents Ca in the sarcoplasmic reticulum. The „slow” compartment contains a significant fraction from the mitochondria. The results indicate that > 40% of cellular Ca can turn over within the period of one contraction cycle. These results are consistent with the following sequence: (1) Upon sarcolemmal depolarization, Ca moves through the Ca channel to arrive at the SR and at the myofilaments. (2) Ca induced Ca release occurs via the „feet” at the SR-inner SL region. The Ca diffuses to the myofilaments or is transported across the SL via the Na-Ca exchanger. (3) Ca is pumped into the free or longitudinal SR and diffuses to the cistemae. Ca is pumped across the SL by the SL Ca pump and by the Na-Ca exchanger. (4) Mitochondrial Ca exchange via the Na-Ca exchanger and/or SL Ca pump. (Supported by NHLBI and the Laubisch and Castera Endowments.)