AJP - Renal Physiology, Vol 255, Issue 6 1170-F1177, Copyright © 1988 by American Physiological Society
Succinate alters respiration, membrane potential, and intracellular K+ in proximal tubule
S. R. Gullans, B. C. Kone, M. J. Avison and G. Giebisch
Renal Division, Brigham and Women's Hospital, Boston, Massachusetts 02115.
Succinate, a dicarboxylic acid, is an intermediate in the Krebs cycle that
is transported and metabolized by the renal proximal tubule. It is also
known to increase proximal tubule transport of phosphate and glucose but
not fluid by unknown mechanisms. In the present study, succinate increased
proximal tubule respiration in a dose-dependent manner, and a kinetic
evaluation indicated that two separate processes were activated. A
lower-affinity (Km = 0.9 mM), higher-capacity stimulation (Vmax increase of
49%) was attributed to a decrease in the mitochondrial coupling efficiency.
A higher-affinity process (Km = 0.012 mM) was related to an apparent
increase in ATP synthesis. The apparent increase in ATP synthesis was not
associated with a change in Na+-K+-ATPase activity, however, but rather
indicated a 49% increase in ion transport-independent ATP utilization.
Basolateral membrane potential hyperpolarized by -7 mV in the presence of
succinate, and this was related to an increase in the K+ transference
number. Finally, 1 and 5 mM succinate promoted a net cellular uptake of K+,
leading to an 11% increase in intracellular K+, which was not the result of
an increase in Na+-K+-ATPase activity. Thus the cellular entry and
metabolism of succinate promotes multiple changes in ion transport without
altering Na+-K+-ATPase activity.
