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Pharmacological evidence for a K ATP channel in renin‐secreting cells from rat kidney
Author(s) -
Russ Ulrich,
Rauch Ulrich,
Quast Ulrich
Publication year - 1999
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1111/j.1469-7793.1999.0781s.x
Subject(s) - hyperpolarization (physics) , membrane potential , chemistry , glibenclamide , biophysics , diazoxide , potassium channel , potassium channel opener , patch clamp , channel blocker , stimulation , endocrinology , medicine , biochemistry , biology , stereochemistry , calcium , receptor , organic chemistry , nuclear magnetic resonance spectroscopy , insulin , diabetes mellitus
1 Openers of the ATP‐sensitive potassium channel (K ATP channel) increase and blockers decrease renin secretion. Here we report the effects of levcromakalim (LCRK, a channel opener) and glibenclamide (GBC, a blocker) on membrane potential, whole‐cell current and the cytoplasmic Ca 2+ concentration of renin‐secreting cells (RSC). Studies were performed on afferent arterioles from the kidney of Na + ‐depleted rats. 2 As monitored with the fluorescent oxonol dye DiBAC 4 (3), LCRK (0.3 and 1 μ m ) induced a hyperpolarization of ≈15 mV which was abolished by GBC (1 μ m ). 3 Whole‐cell current‐clamp experiments showed that RSC had a membrane potential of −61 ± 1 mV ( n = 16 ). LCRK (1 μ m ) induced a hyperpolarization of 9.9 ± 0.2 mV ( n = 16 ) which, in the majority of cells, decreased slowly with time. 4 Capacitance measurements showed a strong electrical coupling of the cells in the preparation. 5 At −60 mV, LCRK induced a hyperpolarizing current in a concentration‐dependent manner with an EC 50 of 152 ± 31 n m and a maximum current of about 200 pA. 6 Application of GBC (1 μ m ) produced no effect; however, when applied after LCRK (300 n m ), GBC inhibited the opener‐induced hyperpolarizing current with an IC 50 of 103 ± 36 n m . 7 LCRK (0.3 and 1 μ m ) did not significantly affect the cytoplasmic Ca 2+ concentration either at rest or after stimulation by angiotensin II. 8 The data show that LCRK induces a GBC‐sensitive hyperpolarizing current in rat RSC. This current presumably originates from the activation of K ATP channels which pharmacologically resemble those in vascular smooth muscle cells. The stimulatory effect of K ATP channel opening on renin secretion is not mediated by a decrease in intracellular Ca 2+ concentration.