ROLE OF MEMBRANE-PERMEABLE IONS IN RENIN SECRETION BY RENAL JUXTAGLOMERULAR CELLS

In this study we examine the role of membrane-permeable ions in renin secretion from renal juxtaglomerular (JG) cells. To this end, extracel lular Cl- (100 mmol/l) in the culture medium of isolated mouse renal J G cells was replaced by the permeable anion NO3- or by the membrane-im permeable anion isethionate. Alternatively, extracellular Na+ (100 mmo l/l) was substituted by the membrane-impermeable cation choline. The e ffects of these ion substitutions on basal and stimulated renin secret ion were then examined. Renin secretion was stimulated by the adenylat e cyclase activator forskolin (10 mu M), the NO donor sodium nitroprus side (SNP, 100 mu M), the calmodulin antagonist calmidazolium (10 mu M ), by lowering extracellular Ca2+ concentration ([Ca2+](e)) with ethyl ene 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, calmidazoliu m, EGTA, or by increased [Ca2+](e). Isethionate, on the other hand, ma rkedly attenuated the effects of EGTA and of increased [Ca2+](e), but not the stimulatory effect of forskolin, calmidazolium, or SNP. Substi tution of Na+ by choline also attenuated basal renin secretion and ren in secretion stimulated by lowering or raising [Ca2+](e). These findin gs suggest that, with respect to the dependency on permeable ions, at least two different pathways of regulated renin secretion from JG cell s exist: a cation- and anion-dependent Ca2+-related pathway and a less ion-sensitive pathway for renin secretion activated by adenosine 3',5 '-cyclic monophosphate and NO.