Reinvestigation of calcium release mechanism from the sarcoplasmic reticulum in cardiac excitation-contraction coupling.

It is generally believed that physiological contraction of mammalian cardiac muscle is mediated by Ca I D12+I D1 released from the sarcoplasmic reticulum(SR)by activation of Ca I D 12+I D 1-induced Ca I D 12+I D 1 release mechanism(CICR)evoked by Ca I D 12+I D 1 entered from external medium during action potentials.However，since inhibitors of CICR appeared not to inhibit cardiac contraction in our preliminary studies，we examined this problem closely.We obtained the following results.1)In the presence of ATP，adenine inhibited CICR also in cardiac muscle as previously shown in Skeletal muscle.2)Adenine up to 10 mM did not inhibit at all electrically evoked cardiac contraction，but only potentietit sly.3.Conversely on washing adenine Ca I D12+I D 1 transient initially increased and then decreased to the original level.4)Procaine inhibited K-induced contraction of cardiac muscle.The results 1)&2)appears to indicate that cardiac contraction is not mediated by CICR，but the immediate effect of adenine on Ca I D 12+I D 1 transient and the result4)clearly support the CICR theory.The apparent discrepancy may be explained by other effects of adenine，inhibition of Ca I D 12+I D 1 uptake by SR and increase of Ca I D 12+I D 1 sensitivity of the contractile system.

It is generally believed that physiological contraction of mammalian cardiac muscle is mediated by CaィイD12+ィエD1 released from the sarcoplasmic reticulum (SR) by activation of CaィイD12+ィエD1 -induced CaィイD12+ィエD1 release mechanism (CICR) evoked by CaィイD12+ィエD1 entered from external medium during action potentials. However, since inhibitors of CICR appeared not to inhibit cardiac contraction in our preliminary studies, we examined this problem closely.We obtained the following results.1) In the presence of ATP, adenine inhibited CICR also in cardiac muscle as previously shown in Skeletal muscle.2) Adenine up to 10 mM did not inhibit at all electrically evoked cardiac contraction, but only potentiated it slowly.3) Adenine initially decreased but then slowly increased action potential-evoked CaィイD12+ィエD1 transient. Conversely on washing adenine CaィイD12+ィエD1 transient initially increased and then decreased to the original level.4) Procaine inhibited K-induced contraction of cardiac muscle.The results 1) & 2) appears to indicate that cardiac contraction is not mediated by CICR, but the immediate effect of adenine on CaィイD12+ィエD1 transient and the result 4) clearly support the CICR theory. The apparent discrepancy may be explained by other effects of adenine, inhibition of CaィイD12+ィエD1 uptake by SR and increase of CaィイD12+ィエD1 sensitivity of the contractile system.