AJP - Renal Physiology, Vol 260, Issue 3 459-F465, Copyright © 1991 by American Physiological Society
Effect of Na-channel blockers and lumen Ca on K secretion by rat renal distal tubule
M. D. Okusa, H. Velazquez and F. S. Wright
Department of Medicine, Yale University School of Medicine, New Haven 06510.
In previous studies the effectiveness of amiloride (AML) in reducing K
secretion has been variable. Based on studies by Cuthbert and Wong (Mol.
Pharmacol. 8: 222-229, 1972) in which the Na-channel-blocking action of AML
in frog skin was found to require the availability of Ca ions in
extracellular fluid, we postulated that the ability of AML and its
analogue, benzamil (BZA), to inhibit distal tubule K secretion depends on
the presence of Ca in luminal fluid. We found that addition of Ca to a
perfusion solution containing 50 microM BZA did reduce K secretion more
than BZA alone. Maximal inhibition was observed with 2.5 mM free ionic Ca.
Graded increases in luminal Ca in presence of AML or BZA reduced K
transport in a dose-dependent manner. The decrease in K secretion with
increasing luminal Ca was paralleled by a decrease in transepithelial
voltage. These results support our hypothesis that the effectiveness of
Na-channel blockers to reduce K secretion by the rat distal tubule depends
on presence of luminal Ca and suggest an interaction between luminal Ca and
Na-channel blockers on the Na channel.
