Original Contribution |
From the Department of Physiology and Pharmacology, Odense University, Odense C, Denmark.
Correspondence to Ulla G. Friis, PhD, Department of Physiology and Pharmacology, Odense University, Winsloewparken 19, 3, DK-5000 Odense C, Denmark. E-mail friis{at}mail.dou.dk
AbstractThe rate of renin
secretion from renal juxtaglomerular (JG) cells is the
major determinant of the activity of the renin-angiotensin
system. However, the 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 kidney to measure changes in cell
membrane capacitance (Cm) as an index of
secretory activity. Resting JG cell Cm was
stable, on average 3.13±0.13 pF (SEM, n=106). In isotonic
solutions, Cm was unaffected by
[Cl-]i. Cm was
consistently increased (7.0±1.3% and 7.2±3.1%) by
intracellular cAMP (1 to 10 µmol/L). This effect was mimicked by
extracellular application of the ß-agonist isoproterenol to the JG
cells (9.4±3.1%). At 100 µmol/L, cAMP induced a paradoxical
decrease in Cm of
20%, which was mimicked
by forskolin. Cell swelling induced by a 7% reduction in osmolality
increased Cm 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
Cm existed. We conclude that the whole-cell
patch-clamp method allows the study of exocytosis and endocytosis in JG
cells. Renin release induced by the cAMP pathway and by cell swelling
is exocytotic, and high-intracellular cAMP levels activate
membrane retrieval mechanisms.
Key Words: juxtaglomerular apparatus renin electrophysiology exocytosis endocytosis cAMP
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