Investigation of factors affecting the intracellular sodium activity in the smooth muscle of guinea‐pig ureter.

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Abstract
1. The intracellular Na+ activity .**GRAPHIC**. of the smooth muscle cells from guinea-pig ureter has been measured using double-barreled Na+-sensitive micro-electrodes. .**GRAPHIC**. in modified Krebs solution at 35.degree. C was of a mean 7.4 .+-. 2.9 mM (n = 32, S.D. of an observation), equivalent to a Na+ equilibrium potential (ENa) of +66.7 mV. Membrane potential (EM) was of a mean -50.8 .+-. 4.6 mV. 2. Inhibition of the Na+ pump by application of ouabain or removal of external K+ .**GRAPHIC**. resulted in a restricted rise of .**GRAPHIC**. The rate of rise was faster in the presence of ouabain (10-4 M) but the stabilized .**GRAPHIC**. was not significantly different from that observed after the prolonged absence of .**GRAPHIC**. The mean .**GRAPHIC**. recorded after prolonged Na+ pump inhibition was 20.6 .+-. 5.5 mM (n = 28), equivalent to an ENa of +39.6 mV. Neither removal of .**GRAPHIC**. after .**GRAPHIC**. had stabilized in the presence of ouabain nor application of ouabain after .**GRAPHIC**. had stabilized in K+-free solution caused a rise in .**GRAPHIC**. suggesting that the Na+ pump was fully inhibited by either procedure. 3. Reduction of .**GRAPHIC**. resulted in a rapid fall in .**GRAPHIC**. against the electrochemical gradient, both before and after Na+ pump inhibition. At each level of .**GRAPHIC**. .**GRAPHIC**. stabilized such that ENa remained approximately constant in either condition. Readdition of .**GRAPHIC**. resulted in a rapid recovery of .**GRAPHIC**. 4. Elevation of .**GRAPHIC**. (at constant .**GRAPHIC**. caused a fall in .**GRAPHIC**. of much the same time course as that observed on reduction of .**GRAPHIC**. both before and after Na+ pump inhibition. The extent of the fall was dependent upon the initial .**GRAPHIC**. Reduction of .**GRAPHIC**. resulted in a rise in .**GRAPHIC**. 5. Elevation of the external cation concentration with Mn2+ or, to a lesser extent, Mg2+ reduced .**GRAPHIC**. in the presence of a functional Na+ pump. But after prolonged exposure to ouabain or K+-free solution, elevation of .**GRAPHIC**. had no effect on .**GRAPHIC**. while application of .**GRAPHIC**. caused a slow rise. These results suggest that .**GRAPHIC**. affects .**GRAPHIC**. in two ways. One is mimicked by Mg2+ and Mn2+ and is probably due to alteration of the Na+ leak. The other is a specific effect, revealed by Na+ pump inhibition. 6. It is concluded that .**GRAPHIC**. can be maintained far from equilibrium in the absence of a functional Na+ pump. Several lines of evidence are discussed which indicate the participation of Na+-Ca2+ exchange in Na+ extrusion in this condition.