Renin release from permeabilized juxtaglomerular cells is stimulated by chloride but not by low calcium

Abstract

The intracellular concentrations of calcium and chloride have been suggested to be involved in the control of renin secretion from juxtaglomerular (JG) cells. We have tested these propositions on permeabilized JG cells. Rat glomeruli with attached JG cells were isolated by the magnetic iron technique, superfused, and permeabilized by 20 microM digitonin for 12 min. The calcium concentration was varied with Ca ethylene glycol-bis (beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) buffers [0 (5 MM EGTA without calcium), 17, 73, 170, 440, or 700 nM and 1.5, 15 or 150 microM]. These maneuvers had no effect on renin release, while 1.5 mM calcium caused a stimulation, which was not inhibited by 50 mM sucrose. Isosmotic increases in the chloride concentration to 25, 60, and 132 mM resulted in prompt stimulations of renin release. Similarly, iodide and nitrate stimulated renin release. We conclude that renin release from permeabilized JG cells is unaffected by calcium concentrations in the nano- and micromolar range, while the release is stimulated by chloride or other permeant anions. We suggest that in intact JG cells an increase in calcium inhibits renin release through activation of chloride channels followed by a drop in the intracellular chloride concentration. The stimulation caused by the high calcium concentration may be a toxic effect or may be due to stimulation of the fusion between granules and cell membrane in a way analogous to other secretory cells.