Dual effect of Na^sub i^+ on Ca^sup 2+^ influx through the Na +/Ca^sup 2+^ exchanger in dialyzed squid axons. Experimental data confirming the validity of the squid axon kinetic model

We propose a steady-state kinetic model for the squid .../... exchanger that differs from other current models of regulation in that it takes into account, within a single kinetic scheme, all ionic [intracellular ... (...)-intracellular ... (...)-intracellular ...] and metabolic (ATP) regulations of the exchanger in which the ...-regulatory pathway plays the central role in regulation. Although the integrated ionic-metabolic model predicts all squid steady-state experimental data on exchange regulation, a critical test for the validity of it is the predicted dual effect of ... on steady-state ... influx through the exchanger. To test this prediction, an improved technique for the estimation of isotope fluxes in squid axons was developed, which allows sequential measurements of ion influx and effluxes. With this method, we report here two novel observations of the squid axon .../... exchanger. First, at intracellular pH (7.0) and in the absence of MgATP, ... has a dual effect on ... influx: inhibition at low concentrations followed by stimulation at high ... concentrations, reaching levels higher than those seen without ... Second, in the presence of MgATP, the biphasic response to ... disappears and is replaced by a sigmoid activation. Furthermore, the model predicts that ... efflux is monotonically inhibited by ..., more pronouncedly without than with MgATP. These results are predicted by the proposed kinetic model. Although not fully applicable to all exchangers, this scheme might provide some insights on expected net ... movements in other tissues under a variety of intracellular ionic and metabolic conditions. (ProQuest: ... denotes formulae/symbols omitted.)