Do Calcium-Activated Chloride Channels Control Renin Secretion?

Physiology ◽  
1990 ◽  
Vol 5 (2) ◽  
pp. 43-46 ◽  
Author(s):  
A Kurtz
Keyword(s):  
Chloride Channels ◽  
Renin Secretion ◽  
Volume Control ◽  
Juxtaglomerular Cells ◽  
Epithelioid Cells ◽  
Intracellular Ca ◽  
Cl Channels

The rate of renin secretion from renal juxtaglomerular epithelioid cells appears to be inversely correlated to intracellular Ca activity. Such a dependency of renin secretion on Ca activity could be controlled by Ca-activated Cl channels that may be involved in the volume control of juxtaglomerular cells.

scholarly journals Cellular control of renin secretion

1999 ◽  
Vol 202 (3) ◽  
pp. 219-225
Author(s):  
A. Kurtz ◽  
C. Wagner
Keyword(s):  
Protein Kinase ◽  
Inhibitory Action ◽  
Second Messengers ◽  
Present Knowledge ◽  
Renin Secretion ◽  
Protein Kinase G ◽  
Juxtaglomerular Cells ◽  
Kinase C ◽  
Cl Channels ◽  
Cellular Control

Renin secretion at the level of renal juxtaglomerular cells appears to be controlled mainly by classic second messengers such as Ca2+, cyclic AMP and cyclic GMP, which in turn exert their effects through oppositely acting protein kinases and probably also by affecting the activity of ion channels in the plasma membrane. Thus, protein kinase A stimulates renin secretion, whilst protein kinase C and protein kinase G II inhibit renin secretion. Moreover, Cl- channels could be involved in the mediation of the inhibitory action of Ca2+ on renin secretion. This review summarizes our present knowledge about the possible actions of these kinases in renal juxtaglomerular cells and considers pathways in the organ control of renin secretion.

Chloride Channels and Salivary Gland Function

1999 ◽  
Vol 10 (2) ◽  
pp. 199-209 ◽  
Author(s):  
J.E. Melvin
Keyword(s):  
Salivary Gland ◽  
Chloride Channels ◽  
Acinar Cells ◽  
Fluid Secretion ◽  
Ductal Cells ◽  
Salivary Gland Cells ◽  
Intracellular Ca ◽  
Cl Channels ◽  
Gland Function ◽  
Induced Changes

Fluid and electrolyte transport is driven by transepithelial Cl- movement. The opening of Cl- channels in the apical membrane of salivary gland acinar cells initiates the fluid secretion process, whereas the activation of Cl- channels in both the apical and the basolateral membranes of ductal cells is thought to be necessary for NaCl re-absorption. Saliva formation can be evoked by sympathetic and parasympathetic stimulation. The composition and flow rate vary greatly, depending on the type of stimulation. As many as five classes of Cl- channels with distinct gating mechanisms have been identified in salivary cells. One of these Cl- channels is activated by intracellular Ca2+, while another is gated by cAMP. An increase in the intracellular free Ca2+ concentration is the dominant mechanism triggering fluid secretion from acinar cells, while cAMP may be required for efficient NaCl re-absorption in many ductal cells. In addition to cAMP- and Ca 2+-gated Cl- channels, agonist-induced changes in membrane potential and cell volume activate different Cl- channels that likely play a role in modulating fluid and electrolyte movement. In this review, the properties of the different types of Cl- currents expressed in salivary gland cells are described, and functions are proposed based on the unique properties of these channels.

Renin secretion from permeabilized juxtaglomerular cells requires a permeant cation

1999 ◽  
Vol 437 (3) ◽  
pp. 449-454 ◽  
Author(s):  
Boye L. Jensen ◽  
Peter Ellekvist ◽  
O. Skøtt
Keyword(s):  
Renin Secretion ◽  
Juxtaglomerular Cells

Hydrogen and potassium regulation of (pro)renin processing and secretion

1994 ◽  
Vol 267 (1) ◽  
pp. F1-F12 ◽  
Author(s):  
J. A. King ◽  
J. C. Fray
Keyword(s):  
Diabetes Mellitus ◽  
Heart Disease ◽  
Surface Membrane ◽  
Endocrine System ◽  
Renin Secretion ◽  
Endocrine Disorders ◽  
K Channels ◽  
Human Renin ◽  
Cl Channels ◽  
H Channels

H and K ions play central roles in prorenin processing and secretion, and prorenin is abnormally expressed in H and K disorders. At the surface membrane of juxtaglomerular (JG) cells, K is sensed and regulated by K channels (coupled to Cl channels and activated by excess Ca), Na-K-adenosinetriphosphatase, and a KCl/H exchange transporter (regulated by Ca). In JG cell granular membrane, K flux is regulated by K channels and a KCl/H exchange transporter (activated by Ca). H channels and a H pump reside in the granular membrane, which maintain H concentration in the granular matrix at least two orders of magnitude greater than in cytosol. The H pump may also be responsible for maintaining the acidic matrix required for maximal prorenin processing to renin by prohormone convertase for human renin (PCren), the prorenin convertase. These molecules form the core of a chemiosmotic system, which appears to regulate both prorenin processing and renin secretion. Renin secretion and prorenin processing appear to be of more than causal significance in clinical disorders characterized by chemiosmotic imbalance. A critical review of the literature supports the following general conclusions. First, hyperrenin state defines the initial phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension. Second, low-renin syndrome defines the transition-to-establish phase in the pathogenesis of heart disease, diabetes mellitus, and hypertension in which the key feature is renin secretory hyporesponsivity. Third, renin disorders are usually associated with other endocrine disorders (polyendocrinopathies types I, II, and III), suggesting that renin may be an important molecule in the processing of chemiosmotic forces. The key chemiosmotic molecules (K and H) are also important in the processing and export of most (if not all) hormones. Thus, by regulating K and H homeostasis, renin may regulate the endocrine system.

Inhibitory effect of calyculin A, a Ser/Thr protein phosphatase type I inhibitor, on renin secretion

1998 ◽  
Vol 275 (5) ◽  
pp. F664-F670 ◽  
Author(s):  
Chun Sik Park ◽  
Mi Hyun Kim ◽  
Chae Hun Leem ◽  
Yeon Jin Jang ◽  
Hae Won Kim ◽  
...  
Keyword(s):  
Okadaic Acid ◽  
Light Chain ◽  
Protein Phosphatase ◽  
Myosin Light Chain ◽  
Renin Secretion ◽  
Type I ◽  
Dependent Manner ◽  
Calyculin A ◽  
Selective Inhibitors ◽  
Intracellular Ca

We have recently shown that several putative selective inhibitors of Ca2+-calmodulin-dependent myosin light chain kinase (MLCK), such as ML-9 [1-(5-chloronaphthalene-1-sulfonyl)-1H-hexahydro-1,4-diazepine], reversibly stimulate renin secretion [C. S. Park, S.-H. Chang, H. S. Lee, S.-H. Kim, J. W. Chang, and C. D. Hong. Am. J. Physiol. 271 ( Cell Physiol. 40): C242–C247, 1996]. We hypothesized that Ca2+ inhibits renin secretion, via phosphorylation of 20-kDa myosin light chain (MLC20), by activating MLCK. In the present studies, we have investigated the types of protein phosphatase (PP) involved in the control of renin secretion through inhibition of MLC dephosphorylation using inhibitors of various types of serine/threonine-specific protein phosphatases. Cyclosporin A, a putative inhibitor of PP type 2 (calcineurin), was without effect. Calyculin A and okadaic acid, putative selective inhibitors of both PP type 1 (PP1) and type 2A (PP2A), significantly inhibited renin secretion under control conditions. Calyculin A had inhibitory effects at least 10-fold more potent than okadaic acid, suggesting that PP1, rather than PP2A, is involved in the control of renin secretion. Furthermore, calyculin A blocked the reversal of renin secretion preinhibited by raised intracellular Ca2+ concentrations in a concentration-dependent manner. Calyculin A (10−6 M) significantly inhibited renin secretion stimulated by lowering intracellular Ca2+ concentrations and blocked the stimulatory effect of ML-9 on renin secretion. Taking all of these results into consideration, we hypothesize that dephosphorylation of MLC20 by Ca2+-independent PP1 stimulates renin secretion, whereas phosphorylation of MLC20 by Ca2+-calmodulin-dependent MLCK inhibits it. This hypothesized regulatory model of renin secretion predicts that the rate of renin secretion at a given time is determined by the ratio of phosphorylated to dephosphorylated MLC20, which is, in turn, determined by the dynamic balance between activity of MLCK and MLC phosphatase.

Low-conductance chloride channels in IEC-6 and CF nasal cells expressing CFTR

1993 ◽  
Vol 264 (3) ◽  
pp. L229-L235
Author(s):  
J. Bijman ◽  
W. Dalemans ◽  
M. Kansen ◽  
J. Keulemans ◽  
E. Verbeek ◽  
...  
Keyword(s):  
Cell Line ◽  
Chloride Channels ◽  
Vero Cells ◽  
Fluid Replacement ◽  
Cystic Fibrosis Gene ◽  
Cl Channel ◽  
Cl Channels ◽  
Excised Patches ◽  
Cloned Cdna ◽  
Cl Permeability

The properties of the cystic fibrosis gene product (CFTR) were studied by expression of cloned cDNA in different cell systems. Infection of both simian fibroblast (Vero) cells and immortalized CF nasal polyp cells (NCF3A) with a vaccinia virus encoding CFTR induced forskolin-induced Cl- permeability and low-conductance (8 pS) Cl- channels. By stable transfection of the rat intestinal crypt-derived cell line IEC-6 we have isolated a clone, IEC-CF7, which expresses CFTR mRNA and antigen. IEC-CF7 cells, but not IEC-6, display forskolin-induced Cl- permeability and multiple linear low-conductance (+/- 8 pS) Cl- channels in cell-attached membrane patches. In excised patches of IEC-CF7 cells, low-conductance Cl- channels could be activated by addition of the catalytic subunit of the adenosine 3',5'-cyclic monophosphate-dependent protein kinase A (PKA) plus ATP. During bath fluid replacement studies, the activated low-conductance channel remained active in the absence of ATP at room temperature and showed saturation kinetics. Rectifying (32 pS) Cl- channels were not observed in either IEC-6 cells or IEC-CF7 cells, indicating that there is no relation between CFTR expression and the incidence of this channel. Our data strongly support the conclusion that CFTR can act as a low-conductance Cl- channel, gated by PKA. The IEC-6-derived cell line IEC-CF7 may prove to be a useful model in the study of CFTR function because of the absence of 32-pS Cl- channel activity and its potential for differentiation.

Chloride channels in apical membrane of primary cultures of rabbit distal bright convoluted tubule

1994 ◽  
Vol 266 (4) ◽  
pp. F543-F553 ◽  
Author(s):  
V. Poncet ◽  
M. Tauc ◽  
M. Bidet ◽  
P. Poujeol
Keyword(s):  
Chloride Channels ◽  
Apical Membrane ◽  
Primary Cultures ◽  
Transmembrane Conductance Regulator ◽  
Patch Clamp Technique ◽  
Cl Channel ◽  
Current Voltage ◽  
Cl Channels ◽  
Inside Out ◽  
Small Conductance

Using the patch clamp technique on the apical membrane of primary cultures of rabbit distal bright convoluted tubule cells (DCTb), two types of Cl- channel were identified. A small channel of 9 pS was observed in 9% of the patches. Cells pretreated with 1 mM 8-bromoadenosine 3',5'-cyclic monophosphate (8-BrcAMP) or 5 microM forskolin increased the expression of Cl- channels by 26 and 37%, respectively. In cell-attached and excised inside-out patches, the current-voltage (I-V) relationships of the 9-pS channel were linear. In only 1 out of 47 active patches was the small-conductance Cl- channel still active 1 h after membrane excision. The addition of 0.1 microM of the catalytic subunit protein kinase A with 2 mM ATP to the cytoplasmic side restored channel activity in 8 out of 15 excised membrane patches. In 5 out of 467 patches of stimulated or nonstimulated cells, a larger Cl- conductance of 30 pS was also recorded. In excised inside-out patches this channel outwardly rectified and was activated by strong depolarization. In cultured DCTb cells, the small-conductance, cAMP-activated Cl- channel shares many properties with the cystic fibrosis transmembrane conductance regulator. Our results suggest that at least the small-conductance channel may participate in Cl- secretion across the apical membrane of DCTb in primary culture. This secretion may increase the rate of the apical Cl-/HCO3- exchange indirectly by enhancing the inwardly-directed Cl- gradient.

scholarly journals Volume-regulated Cl− current: contributions of distinct Cl− channels and localized Ca2+ signals

2019 ◽  
Vol 317 (3) ◽  
pp. C466-C480 ◽  
Author(s):  
Yani Liu ◽  
Huiran Zhang ◽  
Hongchao Men ◽  
Yuwei Du ◽  
Ziqian Xiao ◽  
...  
Keyword(s):  
Anion Channel ◽  
Fluorescent Imaging ◽  
Hek293 Cells ◽  
Cell Swelling ◽  
Anoctamin 1 ◽  
Component Cell ◽  
Intracellular Ca ◽  
Cl Channels ◽  
A Cell ◽  
Necessary And Sufficient

The swelling-activated chloride current ( ICl,swell) is induced when a cell swells and plays a central role in maintaining cell volume in response to osmotic stress. The major contributor of ICl,swell is the volume-regulated anion channel (VRAC). Leucine-rich repeat containing 8A (LRRC8A; SWELL1) was recently identified as an essential component of VRAC, but the mechanisms of VRAC activation are still largely unknown; moreover, other Cl− channels, such as anoctamin 1 (ANO1), were also suggested to contribute to ICl,swell. In this present study, we investigated the roles of LRRC8A and ANO1 in activation of ICl,swell; we also explored the role of intracellular Ca2+ in ICl,swell activation. We used a CRISPR/Cas9 gene editing approach, electrophysiology, live fluorescent imaging, selective pharmacology, and other approaches to show that both LRRC8A and ANO1 can be activated by cell swelling in HEK293 cells. Yet, both channels contribute biophysically and pharmacologically distinct components to ICl,swell, with LRRC8A being the major component. Cell swelling induced oscillatory Ca2+ transients, and these Ca2+ signals were required to activate both the LRRC8A- and ANO1-dependent components of ICl,swell. Both ICl,swell components required localized rather than global Ca2+ for activation. Interestingly, while intracellular Ca2+ was necessary and sufficient to activate ANO1, it was necessary but not sufficient to activate LRRC8A-mediated currents. Finally, Ca2+ transients linked to the ICl,swell activation were mediated by the G protein-coupled receptor-independent PLC isoforms.

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