The effect of ATP and other nucleotides on calcium efflux was studied in squid axons dialyzed with Ca:ethylene glycol tetraacetic acid buffers to control the internal ionized calcium concentration. In the virtual absence of internal ATP (ca. 1 muM) a significant level of calcium efflux occurs which could be increased by the addition of internal ATP. At low concentrations of ionized calcium (ca. 200 nM), efflux increased 10-fold. At high levels of ionized calcium (ca. 100 muM), the increase was only twofold. This stimulation of efflux by ATP requires internal sodium. Conversely, ATP renders the calcium efflux insensitive to internal sodium and prevents the inhibition of calcium efflux produced by internal sodium in the absence of ATP. Of 12 nucleotides tested, only ATP, deoxy-ATP and alpha, beta-methylene ATP significantly stimulated calcium efflux. The data are interpreted as indicating that ATP induces an affinity in change in the carrier system binding calcium to the internal site, possibly by a phosphorylating step.
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