Role of membrane-permeable ions in renin secretion by renal juxtaglomerular cells

Abstract

In this study we examine the role of membrane-permeable ions in renin secretion from renal juxtaglomerular (JG) cells. To this end, extracellular Cl- (100 mmol/l) in the culture medium of isolated mouse renal JG cells was replaced by the permeable anion NO3- or by the membrane-impermeable anion isethionate. Alternatively, extracellular Na+ (100 mmol/l) was substituted by the membrane-impermeable cation choline. The effects of these ion substitutions on basal and stimulated renin secretion were then examined. Renin secretion was stimulated by the adenylate cyclase activator forskolin (10 microM), the NO donor sodium nitroprusside (SNP, 100 microM), the calmodulin antagonist calmidazolium (10 microM), by lowering extracellular Ca2+ concentration ([Ca2+]e) with ethylene glycol-bis(beta-aminoethyl ether)-N,N,N',N'-tetraacetic acid (EGTA) (2 mM), and by increasing [Ca2+]e from the normal value of 0.5 to 3 mM. Substitution of extracellular Cl- by isethionate, but not by NO3-, inhibited basal renin release over 20 h of incubation. NO3- also did not change renin secretion stimulated by forskolin, SNP, calmidazolium, EGTA, or by increased [Ca2+]e. Isethionate, on the other hand, markedly attenuated the effects of EGTA and of increased [Ca2+]e, but not the stimulatory effect of forskolin, calmidazolium, or SNP. Substitution of Na+ by choline also attenuated basal renin secretion and renin secretion stimulated by lowering or raising [Ca2+]e. These findings suggest that, with respect to the dependency on permeable ions, at least two different pathways of regulated renin secretion from JG cells exist: a cation- and anion-dependent Ca(2+)-related pathway and a less ion-sensitive pathway for renin secretion activated by adenosine 3',5'-cyclic monophosphate and NO.