Electrochemical ion gradients and the Na/Ca exchange stoichiometry. Measurements of these gradients are thermodynamically consistent with a stoichiometric coefficient greater than or equal to 3

Dear Sir: With ion-selective microelectrodes, it is possible to measure intracellular ion activities and calculate transmembrane electrochemical potential differences. Recently, these techniques have been carefully applied to the measurement of Na and Ca ion activities in mammalian ventricular and Purkinje fibers (Sheu and Fozzard, 1982). The results show that under a wide variety of circumstances the ratio of the electrochemical gradients for Na and Ca remains remarkably constant near a value of 2.5. It is reasonable under certain conditions to expect that this ratio represents the stoichiometric coefficient of the Na/Ca exchange. Nonetheless, we wish to point out certain difficulties inherent in the derivation of the exchange stoichi-ometry from such measurements. In addition, we wish to discuss Sheu and Fozzard's intriguing observation that the ratio increases to ^-3 when the Na pump is inhibited. We hypothesize that exchange may be represented by the following transmem-brane reaction : where n is a stoichiometric coefficient and "i" and "o" designate intracellular and extracellular ions, respectively. The driving force for this reaction is given by : A = n A~Na-01", (2) where A is the electrochemical affinity and Ak is the transmembrane electro-chemical potential difference .' When A = 0, equilibrium exists and no net transport of ions occurs via exchange. As recognized by Sheu and Fozzard, such a condition must exist for A%sCa/AuN. to equal n. ' We shall use the notational conventions of Sheu and Fozzard (1982), namely that positive O~ is an inwardly directed electrochemical gradient. Accordingly, positive values of A imply forward progress of reaction 1 .