Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

The cytosolic concentration of chloride correlates directly with renin secr etion from renal juxtaglomerular granular (JG) cells. In the present study, the mechanism by which chloride stimulates renin release was investigated in a preparation of permeabilized rat glomeruli with attached JG cells. An isosmotic increase in the concentration of chloride by 129 mM stimulated re nin release 16- to 20-fold. Substitution of K+ by the impermeant cation N-m ethyl-D-glucamine (NMDG) abolished this response, while substitution with N a+ caused marginal inhibition. Substitution with Cs+ had no effect. Additio n of sucrose, which permeates the secretory granules poorly, also abolished the stimulation of renin secretion by KCl. The response to KCl was not aff ected by K+-channel antagonists or by agonists of K+ channels. Chloride cha nnel blockers were also without effect on the secretory response to KCl. Wh en the ATP concentration was lowered from 1 to 0.1 mM renin release was sti mulated, while an increase in the ATP concentration from 1 to 5 mM had no e ffect. Blockers of ATP-sensitive (K-ATP) channels did not modify the respon se to chloride. The present data suggest that chloride stimulates renin rel ease after entry of KCl into the renin secretory granules which results in swelling and release of renin.