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  • Title: Pharmacological evidence for a KATP channel in renin-secreting cells from rat kidney.
    Author: Russ U, Rauch U, Quast U.
    Journal: J Physiol; 1999 Jun 15; 517 ( Pt 3)(Pt 3):781-90. PubMed ID: 10358118.
    Abstract:
    1. Openers of the ATP-sensitive potassium channel (KATP 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 Ca2+ 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 DiBAC4(3), LCRK (0.3 and 1 microM) induced a hyperpolarization of approximately 15 mV which was abolished by GBC (1 microM). 3. Whole-cell current-clamp experiments showed that RSC had a membrane potential of -61 +/- 1 mV (n = 16). LCRK (1 microM) 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 EC50 of 152 +/- 31 nM and a maximum current of about 200 pA. 6. Application of GBC (1 microM) produced no effect; however, when applied after LCRK (300 nM), GBC inhibited the opener-induced hyperpolarizing current with an IC50 of 103 +/- 36 nM. 7. LCRK (0.3 and 1 microM) did not significantly affect the cytoplasmic Ca2+ 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 KATP channels which pharmacologically resemble those in vascular smooth muscle cells. The stimulatory effect of KATP channel opening on renin secretion is not mediated by a decrease in intracellular Ca2+ concentration.
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