An investigation of sodium-calcium exchange in the smooth muscle of guinea-pig ureter.

1. After application of ouabain (10(-4) M), the intracellular Na+ activity (alpha iNa) of smooth muscle cells in the guinea-pig ureter stabilizes at a relatively low level which can be rapidly lowered by reduction of external Na+ (Na+o) or elevation of Ca2+o. Both these procedures also elicit a transient contracture. These observations have previously been interpreted as evidence for Na+-Ca2+ exchange. The presence of such an exchange mechanism has now been further investigated by measurements of alpha iNa, tension, ion analysis and 22Na efflux. 2. Ion analysis demonstrated that tissues were able to maintain a high cellular K+ content in the presence of ouabain, but slowly lost K+ and gained Na+ if K+o was also removed, as expected for an infinite outward gradient for K+ and a fully inhibited Na+ pump. 3. Tissues were only able to maintain a low cellular Na+ and high cellular K+ in the presence of ouabain if Ca2+ was present in the bathing solution. Reduction of Ca2+o to very low levels also caused a continual slow rise in alpha iNa in the presence of ouabain, provided that the prolonged depolarization caused by these low levels was prevented by elevation of Mg2+o. Alteration of the membrane potential by changing K+o at constant Na+o showed that alpha iNa decreased by about 1.2 mM for a 10 mV depolarization, within the range from -70 to -30 mV. 4. A small Ca2+o-activated 22Na efflux was observed in ouabain-treated tissues in the absence of Na+o. 40 mM-Ca2+ was not more effective at activating this efflux than was 2.5 mM-Ca2+, while 40 mM-Mg2+ was ineffective. Restoration of the normal Na+o caused a large increase in the rate of 22Na loss. 5. Application of Mn2+ in the presence of ouabain caused a slow rise in alpha iNa and a small decline in resting tension. The fall in alpha iNa on reduction of Na+o was slowed by the presence of Mn2+ (mean half-time increased from 1.7 to 5.0 min) and the concomitant contracture was almost abolished. These results are consistent with a Mn2+-induced inhibition of Na+-Ca2+ exchange. However, the fall in alpha iNa induced by elevation of Ca2+o was unaffected by the presence of Mn2+ and the attendant contracture was, if anything, enhanced. 6. Observation of changes in alpha iNa and tension at various Mn2+ and Ca2+ concentrations demonstrated a competitive interaction between the two divalent cations.(ABSTRACT TRUNCATED AT 400 WORDS)