Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

Abstract

The cytosolic concentration of chloride correlates directly with renin secretion from renal juxtaglomerular granular (JG) cells. In the present study, the mechanism by which chloride stimulates renin release was investigated in a preparation of permeabilized rat glomeruli with attached JG cells. An isosmotic increase in the concentration of chloride by 129 mM stimulated renin release 16- to 20-fold. Substitution of K+ by the impermeant cation N-methyl-d-glucamine (NMDG) abolished this response, while substitution with Na+ caused marginal inhibition. Substitution with Cs+ had no effect. Addition of sucrose, which permeates the secretory granules poorly, also abolished the stimulation of renin secretion by KCl. The response to KCl was not affected by K+-channel antagonists or by agonists of K+ channels. Chloride channel blockers were also without effect on the secretory response to KCl. When the ATP concentration was lowered from 1 to 0.1 mM renin release was stimulated, while an increase in the ATP concentration from 1 to 5 mM had no effect. Blockers of ATP-sensitive (KATP) channels did not modify the response to chloride. The present data suggest that chloride stimulates renin release after entry of KCl into the renin secretory granules which results in swelling and release of renin.

Molecular and Functional Identification of Cyclic AMP-Sensitive BK Ca Potassium Channels (ZERO Variant) and L-Type Voltage-Dependent Calcium Channels in Single Rat Juxtaglomerular Cells

“…Anisosmotic addition of K ϩ leads to transient shrinkage and inhibition of renin release. 26 During stimulation of renin release by maneuvers that increase the cellular cAMP concentration (sympathetic nervous activity, prostaglandin E2, dopamine, etc), the concomitant activation of the BK Ca channels may protect the cells against depolarization and activation of VDCCs. When acute depolarization occurs, the calcium influx may inhibit renin release, but activation of the BK Ca channels may repolarize the cells and terminate the inhibitory signal.…”

Cellular mechanism of renin release

“…As chloride is essential for the swelling of the renin containing granules, which in turn precedes exocytosis, Cl − efflux from the cytosol also inhibits renin release. Support for the assumption that chloride channels are involved in the control of renin release by calcium is provided by studies demonstrating that chloride per se stimulates renin release from intact as well as from permeabilized JG cells (Skott & Jensen 1992, Jensen & Skott 1994, Jensen et al. 1999), whilst the inhibitory effect of calcium requires electrically intact cells.…”

Role of potassium channels in the control of renin secretion from isolated perfused rat kidneys

“…Following the observation that shrinking JG cells in vitro is associated with inhibition of renin secretion [7], it was hypothesized that calcium could determine the cell volume of JG cells by regulating KCl efflux triggered by the activity of chloride channels [17]. A loss of KCl could also be relevant to renin secretion independently of cell volume changes, because intracellular chloride and potassium both appear to be essential for inducing exocytosis in JG cells [12,15]. Electroneutral KCl efflux from JG cells essentially involves potassium channel activity in conjunction with chloride channel activity [17].…”