Direct demonstration of exocytosis and endocytosis in single mouse juxtaglomerular cells

The rate of renin secretion from renal juxtaglomerular (JG) cells is the ma jor determinant of the activity of the renin-angiotensin system. However, t he mechanisms involved in the excretion and turnover of secretory granules in the JG cells remain obscure. Therefore, in the present study, the whole- cell patch-clamp technique was applied to single JG cells from the mouse ki dney to measure changes in cell membrane capacitance (C-m) as an index of s ecretory activity. Resting JG cell C-m was stable, on average 3.13+/-0.13 p F (SEM, n=106). In isotonic solutions, C-m was unaffected by [Cl-](i). C-m was consistently increased (7.0+/-1.3% and 7.2+/-3.1%) by intracellular cAM P (1 to 10 mu mol/L). This effect was mimicked by extracellular application of the P-agonist isoproterenol to the JG cells (9.4+/-3.1%). At 100 mu mol /L, cAMP induced a paradoxical decrease in C-m of less than or equal to 20% , which was mimicked by forskolin. Cell swelling induced by a 7% reduction in osmolality increased C-m with no significant additional effects to [Cl-] (i) and cAMP. cAMP increased whole-cell outward current 2- to 4-fold in all groups, but no correlation between changes in whole-cell currents and C-m existed. We conclude that the whole-cell patch-clamp method allows the stud y of exocytosis and endocytosis in JG cells. Renin release induced by the c AMP pathway and by cell swelling is exocytotic, and hi,oh-intracellular cAM P levels activate membrane retrieval mechanisms.