1. Mammalian heart muscle is extremely sensitive to the external calcium concentration. It reacts to alterations of the external calcium concentration with an immediate adaptation of contractile force. 2. In mammalian heart there is a network of large transverse tubules throughout the cell. These structures are regularly arranged at the level of the sarcomeric Z- and I-lines and increase the cell surface by a factor of ten. 3. Experimental evidence favours the assumption that the plasmalemma could be the site of a loosely bound superficial Ca fraction which becomes ionized upon depolarization and is again bound upon repolarization of the cardiac cell membrane. 4. A mechanism is discussed which bases the excitation-contraction coupling process on a physicochemical interaction of calcium with membrane phospholipids. The degree of interaction is thought to be governed by the transmembrane electric field, the induced dipole moment of membrane constituents, and proton activity within the membrane.

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Uptake and displacement of [3H]-propranolol and [3H]-chlorpromazine in isolated, recirculating perfused guinea-pig lungs.

The pulmonary uptake of tritium labelled propranolol and chlorpromazine and their displacement by amphiphilic drugs has been studied in isolated guinea-pig lungs. Lungs were perfused by recirculation with 60 ml tyrode solution (carbogen gassed, 37 degrees C, 6% hydroxy-ethyl-starch) at a flow rate of 10 ml/min. In uptake experiments, a steady state was reached within 20 min with 95% of 10(-9) M propranolol and 90% of 10(-9) M chlorpromazine removed from the perfusate. Using 10(-4) M propranolol, a saturation process became evident, whereas no concentration dependency was observed for chlorpromazine uptake. Kinetic analysis revealed similar uptake rates, but different capacities for both compounds. In displacement experiments, 10(-9) M propranolol was displaced by 10(-4) M amphiphilic drugs in the order: chlorpromazine greater than propranolol greater than alprenolol greater than tetracaine. No displacement occurred by practolol, indomethacin or phenylbutazone. The results indicate that the lungs have a large binding capacity for amphiphilic drugs. These compounds can interfere with each other, according to their lipophilicity, their steric configuration and charges.

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