It is well known that the immunosuppressant cyclosporine A (CsA) stimulates the renin-angiotensin system, but the mechanism behind remains obscure. Cyclosporine A is an inhibitor of the calcium-activated phosphatase calcineurin, and it is possible that CsA exerts its effect on renin release through a direct effect in juxtaglomerular (JG)-cells. The aim of this study was to determine the effect of CsA on renin secretion, using electrophysiological methods on single rat JG cells. Membrane capacitance (Cm) was recorded as a measure of exocytosis. Results: Extracellular application of CsA (5 μM) increased membrane capacitance (Cm) by 10.7% ± 2.9% (n=5; P<0.05). When the experiments were repeated with a PKA-blocker (RpcAMPs (5 μM)) in the patch pipette, CsA (5 μM) still increased membrane capacitance significantly (15.8% ± 4.2% (n=4)), indicating that the increase in exocytosis is independent on the cAMP-PKA-pathway. The effect of CsA could be mimicked by chelating intracellular calcium using EGTA (0.1 mM) in the patch pipette. Under these experimental conditions, membrane capacitance increased 12.4% ± 3% (n=3). Addition of CsA (5 μM) did not result in any further increase in Cm (amounting to 11.8% ± 4.7% (n=3)), indicating a common signal transduction pathway. Conclusions Lowering intracellular calcium and cyclosporine A have common effects on Cm which could be due to calcineurin inhibition. In addition, calcineurin exerts a tonic supressor effect on renin release from juxtaglomerular cells. This study was supported by grants from Carlsbergfondet, the Novo Nordisk Foundation and the Danish Heart Foundation.