EFFECT OF NA-CHANNEL BLOCKERS AND LUMEN CA ON K SECRETION BY RAT RENAL DISTAL TUBULE

In previous studies the effectiveness of amiloride (AML) in reducing K secretion has been variable. Based on studies by Cuthbert and Wong (Mol. Pharmaco. 8: 222-229, 1972) in which the Nachannel-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-mu-M 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.