Studies of the sodium-calcium exchanger in bull-frog atrial myocytes

1. Experimental measurements and computer simulations have been used in attempts to identify an exchanger current (Iex) generated by an electrogenic Na+-Ca2+ exchanger in single cells from bull-frog atrium. 2. Voltage clamp measurements of an inward 'slow tail' current observed upon repolarization after depolarizing clamp pulses that elicit net inward Ca2+ currents (ICa) (see Campbell, Giles & Shibata, 1988c), show that these slow tails have a cationic dependence different from ICa. Slow tails are large and prominent in normal [Na+]o solutions containing either Ca2+ or Sr2+, but they are markedly reduced or absent in Ba2+, Ca2+-free, and Na+-free solutions. 3. Kinetic measurements on the slow tails show that they are not generated by deactivation of ICa, and suggest that they may be due to activation of Iex at negative potentials (-70 to -100 mV). 4. Computer simulations of the influx, buffering, and extrusion of Ca2+ provide further indirect evidence that the slow tails correspond to Iex. In addition, these calculations give insights into one plausible mechanism of Ca2+ homeostasis in frog atrium. When the Na+-Ca2+ exchanger formalism of Mullins (1979, 1981), as modified by DiFrancesco & Nobel (1985), is combined with equations for intracellular Ca2+ buffering by myoplasmic proteins (cf. Robertson, Johnson & Potter, 1981), slow inward tails are produced which are qualitatively similar to those recorded experimentally. 5. Comparisons of the size and time course of ICa with those of Iex suggest that Iex does not generate a physiologically significant current (or membrane potential change) during the plateau of the action potential. However, at potentials near the resting potential the inward current due to Iex may be significant. 6. Our theoretical results suggest that in the intact single atrial cell myoplasmic Ca2+-binding proteins (e.g. calmodulin and troponin) could be physiologically important modulators of the amplitude, polarity and kinetics of Iex. Hence, the specificity, capacity and kinetics of intracellular Ca2+ binding are essential components of any quantitative treatment of Iex in excitable tissue.