Modulation of voltage-dependent Ca2+ conductance by changing Cl- concentration in rat lactotrophs

1997 ◽  
Vol 272 (4) ◽  
pp. C1178-C1185 ◽  
Author(s):  
L. Garcia ◽  
M. Fahmi ◽  
N. Prevarskaya ◽  
B. Dufy ◽  
P. Sartor
Keyword(s):  
Carboxylic Acid ◽  
Fluorescence Probe ◽  
Physiological Role ◽  
Feedback Mechanism ◽  
Pituitary Cells ◽  
Physiological Processes ◽  
Voltage Dependent ◽  
Ca2 Channels ◽  
Cl Conductance

In pituitary cells, voltage-dependent Ca2+ channels play an important role in such physiological processes as exocytosis, secretion, the cell cycle, and proliferation. Thus mechanisms that modulate voltage-dependent Ca2+ channel activity participate indirectly in regulating intracellular Ca2+ concentration. We have shown a new modulating mechanism for voltage-dependent Ca2+ channels by demonstrating that Ca2+ influx is influenced by Cl-. To evaluate the role of Cl- on Ca2+ conductance coupling, we first measured the intracellular Cl- concentration of rat lactotrophs using the Cl(-)-sensitive fluorescence probe sulfopropylquinolinium by simple microspectrofluorometry or combined with electrophysiology. We found an average intracellular Cl- concentration of rat lactotrophs of approximately 60 mM (n = 39). Using the whole cell tight-seal recording technique, we showed that a reduction in external Cl- concentration ([Cl-]o) and a decrease in Cl- conductances affected Ca2+ conductance as measured by Ba2+ movement through the Ca2+ channels (I(Ba)). Low [Cl-]o (39 mM) induced a decrease in Ca2+ entry via voltage-gated Ca2+ channels (-27.75 +/- 4% of normalized I(Ba)). Similarly, blockade of the Cl- conductance by 1 mM 9-anthracene carboxylic acid induced a decrease in I(Ba) (-26 +/- 6% of normalized I(Ba)). This modulation of I(Ba) was inhibited by 24-h pretreatment of the cells with pertussis toxin (1 microg/ml), suggesting that changes in Cl- concentration induced by low [Cl-]o and 9-anthracene carboxylic acid interfered with the phosphorylation of G proteins involved in Ca2+ channel activation. These results suggest a feedback mechanism based on constant interaction between Ca2+ and Cl-. Finally, they also emphasize the physiological role of Cl- in rat lactotrophs.

Role of Ca2+ and Na+ on luteinizing hormone release from the calf pituitary

1988 ◽  
Vol 255 (4) ◽  
pp. E469-E474
Author(s):  
J. P. Kile ◽  
M. S. Amoss
Keyword(s):  
Luteinizing Hormone ◽  
Ionophore A23187 ◽  
Channel Blockers ◽  
Hormone Release ◽  
Primary Cells ◽  
Rat Pituitary ◽  
Voltage Dependent ◽  
Lh Release ◽  
Ca2 Channels

It has been proposed that gonadotropin-releasing hormone (GnRH) stimulates Ca2+ entry by activation of voltage-independent, receptor-mediated Ca2+ channels in the rat gonadotroph. Little work has been done on the role of calcium in GnRH-induced luteinizing hormone (LH) release in species other than the rat. Therefore, this study was done to compare the effects of agents that alter Ca2+ or Na+ entry on LH release from calf anterior pituitary primary cells in culture. GnRH (100 ng/ml), Ca2+ ionophore A23187 (2.5 microM), and the depolarizing agent ouabain (0.1-10 microM) all produced significant increases (P less than 0.05) in LH release; these effects were significantly reduced when the cells were preincubated with the organic Ca2+ channel blockers nifedipine (1-10 microM) and verapamil (1-10 microM) and with Co2+ (0.01-1 mM). The effect of ouabain was inhibited by tetrodotoxin (TTX; 1-10 nM) as well as by nifedipine at 0.1-10 microM. In contrast to its effect on rat pituitary LH release, TTX significantly inhibited GnRH-stimulated LH release at 1-100 nM. These results suggest that GnRH-induced LH release may employ Ca2+ as a second messenger in bovine gonadotrophs and support recent speculation that GnRH-induced Ca2+ mobilization may in part be voltage dependent.

scholarly journals Studies on the Physiological Role of Hypothalamic TRH on the Negative Feedback Mechanism of the Pituitary-Thyroid Axis

1979 ◽  
Vol 55 (6) ◽  
pp. 776-786
Author(s):  
Masatomo MORI ◽  
Kihachi OHSHIMA ◽  
Sakae MARUTA ◽  
Hitoshi FUKUDA ◽  
Yohnosuke SHIMOMURA ◽  
...  
Keyword(s):  
Negative Feedback ◽  
Physiological Role ◽  
Feedback Mechanism ◽  
Negative Feedback Mechanism ◽  
Pituitary Thyroid Axis ◽  
Thyroid Axis

scholarly journals Ca2+ signaling evoked by activation of Na+ channels and Na+/Ca2+ exchangers is required for GABA-induced NG2 cell migration

2009 ◽  
Vol 186 (1) ◽  
pp. 113-128 ◽  
Author(s):  
Xiao-ping Tong ◽  
Xiang-yao Li ◽  
Bing Zhou ◽  
Wanhua Shen ◽  
Zhi-jun Zhang ◽  
...  
Keyword(s):  
Gabaa Receptors ◽  
Physiological Role ◽  
Brain Regions ◽  
Na Channels ◽  
Typical Action ◽  
Sequential Activation ◽  
Ng2 Cells ◽  
And Function ◽  
Ca2 Channels

NG2 cells originate from various brain regions and migrate to their destinations during early development. These cells express voltage-gated Na+ channels but fail to produce typical action potentials. The physiological role of Na+ channels in these cells is unclear. We found that GABA induces membrane depolarization and Ca2+ elevation in NG2 cells, a process requiring activation of GABAA receptors, Na+ channels, and Na+/Ca2+ exchangers (NCXs), but not Ca2+ channels. We have identified a persistent Na+ current in these cells that may underlie the GABA-induced pathway of prolonged Na+ elevation, which in turn triggers Ca2+ influx via NCXs. This unique Ca2+ signaling pathway is further shown to be involved in the migration of NG2 cells. Thus, GABAergic signaling mediated by sequential activation of GABAA receptors, noninactivating Na+ channels, and NCXs may play an important role in the development and function of NG2 glial cells in the brain.

scholarly journals Is there a role for T-type Ca2+ channels in regulation of vasomotor tone in mesenteric arterioles?This article is part of a Special Issue on Information Transfer in the Microcirculation.

2009 ◽  
Vol 87 (1) ◽  
pp. 8-20 ◽  
Author(s):  
Lars Jørn Jensen ◽  
Niels-Henrik Holstein-Rathlou
Keyword(s):  
Information Transfer ◽  
Electromechanical Coupling ◽  
Low Voltage ◽  
Vasomotor Tone ◽  
Direct Demonstration ◽  
Voltage Dependent ◽  
Small Conductance ◽  
Ca2 Channels ◽  
Peripheral Blood Pressure

The largest peripheral blood pressure drop occurs in terminal arterioles (<40 µm lumen diameter). L-type voltage-dependent Ca2+ channels (VDCCs) are considered the primary pathway for Ca2+ influx during physiologic activation of vascular smooth muscle cells (VSMC). Recent evidence suggests that T-type VDCCs are expressed in renal afferent and efferent arterioles, mesenteric arterioles, and skeletal muscle arterioles. T-type channels are small-conductance, low voltage-activated, fast-inactivating channels. Thus, their role in supplying Ca2+ for contraction of VSMC has been disputed. However, T-type channels display non-inactivating window currents, which may play a role in sustained Ca2+ entry. Here, we review the possible role of T-type channels in vasomotor tone regulation in rat mesenteric terminal arterioles. The CaV3.1 channel was immunolocalized in VSMC, whereas the CaV3.2 channel was predominantly expressed in endothelial cells. Voltage-dependent Ca2+ entry was inhibited by the new specific T-type blockers R(–)-efonidipine and NNC 55-0396. The effect of NNC 55-0396 persisted in depolarized arterioles, suggesting an unusually high activation threshold of mesenteric T-type channels. T-type channels were not necessary for conduction of vasoconstriction, but appear to be important for local electromechanical coupling in VSMC. The first direct demonstration of endothelial T-type channels warrants new investigations of their role in vascular biology.

scholarly journals The role of integrins αv in the pathogenesis of oral squamous cell carcinoma

2019 ◽  
Vol 5 (4) ◽  
pp. 86-93
Author(s):  
G. M. Tuguzbaeva ◽  
V. N. Pavlov
Keyword(s):  
Squamous Cell Carcinoma ◽  
Oral Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Physiological Role ◽  
Normal Epithelium ◽  
Molecular Oncology ◽  
Physiological Processes ◽  
Integrin Family

The initiation of carcinoma progression is attributed to significant disorders in the synthesis of macromolecules that affect physiological processes in the epithelial cells of oral mucosa. It is known that the integrin family receptors are crucial for regenerative and reparative functions of the normal epithelium. In addition to their well-established physiological role, some types of integrins are the major determinants of malignant transformations. In particular, the results of recent studies in molecular oncology reveal the importance of αv integrins in the pathogenesis of carcinomas, including oral squamous cell carcinoma. This review aims to analyse the significance of αv integrins in the key processes of malignant growth and metastasis of oral squamous cell carcinoma. The prospects of using αv integrins as prognostic molecular markers and targets for developing novel diagnostic and therapeutic methods in the management of oral cancer are discussed.

Characterizing voltage-dependent Ca2+ channels coupled to VIP release and NO synthesis in enteric synaptosomes

2002 ◽  
Vol 283 (5) ◽  
pp. G1027-G1034 ◽  
Author(s):  
M. Kurjak ◽  
A. Sennefelder ◽  
M. Aigner ◽  
V. Schusdziarra ◽  
H. D. Allescher
Keyword(s):  
Nitric Oxide ◽  
No Synthase ◽  
Channel Blockers ◽  
Voltage Dependent ◽  
Intracellular Ca ◽  
P Type ◽  
Ca2 Channels

In enteric synaptosomes of the rat, the role of voltage-dependent Ca2+channels in K+-induced VIP release and nitric oxide (NO) synthesis was investigated. Basal VIP release was 39 ± 4 pg/mg, and cofactor-substituted NO synthase activity was 7.0 ± 0.8 fmol · mg−1 · min−1. K+ depolarization (65 mM) stimulated VIP release Ca2+ dependently (basal, 100%; K+, 172.2 ± 16.2%; P < 0.05, n = 5). K+-stimulated VIP release was reduced by blockers of the P-type (ω-agatoxin-IVA, 3 × 10−8 M) and N-type (ω-conotoxin-GVIA, 10−6 M) Ca2+ channels by ∼50 and 25%, respectively, but not by blockers of the L-type (isradipine, 10−8 M), Q-type (ω-conotoxin-MVIIC, 10−6 M), or T-type (Ni2+, 10−6 M) Ca2+ channels. In contrast, NO synthesis was suppressed by ω-agatoxin-IVA, ω-conotoxin-GVIA, and isradipine by ∼79, 70, and 70%, respectively, whereas Ni2+ and ω-conotoxin-MVIIC had no effect. These findings are suggestive of a coupling of depolarization-induced VIP release primarily to the P- and N-type Ca2+ channels, whereas NO synthesis is presumably dependent on Ca2+ influx not only via the P- and N- but also via the L-type Ca2+ channel. In contrast, none of the Ca2+ channel blockers affected VIP release evoked by exogenous NO, suggesting that NO induces VIP secretion by a different mechanism, presumably involving intracellular Ca2+ stores.

scholarly journals Exploring a role for heteromerization in GPCR signalling specificity

2010 ◽  
Vol 433 (1) ◽  
pp. 11-18 ◽  
Author(s):  
Raphael Rozenfeld ◽  
Lakshmi A. Devi
Keyword(s):  
Physiological Role ◽  
Therapeutic Effects ◽  
Receptor Ligands ◽  
Physiological Processes ◽  
Downstream Effectors ◽  
Signal Specificity ◽  
G Protein Coupled ◽  
Intracellular Milieu ◽  
Formation Of Complexes

The critical involvement of GPCRs (G-protein-coupled receptors) in nearly all physiological processes, and the presence of these receptors at the interface between the extracellular and the intracellular milieu, has positioned these receptors as pivotal therapeutic targets. Although a large number of drugs targeting GPCRs are currently available, significant efforts have been directed towards understanding receptor properties, with the goal of identifying and designing improved receptor ligands. Recent advances in GPCR pharmacology have demonstrated that different ligands binding to the same receptor can activate discrete sets of downstream effectors, a phenomenon known as ‘ligand-directed signal specificity’, which is currently being explored for drug development due to its potential therapeutic advantage. Emerging studies suggest that GPCR responses can also be modulated by contextual factors, such as interactions with other GPCRs. Association between different GPCR types leads to the formation of complexes, or GPCR heteromers, with distinct and unique signalling properties. Some of these heteromers activate discrete sets of signalling effectors upon activation by the same ligand, a phenomenon termed ‘heteromer-directed signalling specificity’. This has been shown to be involved in the physiological role of receptors and, in some cases, in disease-specific dysregulation of a receptor effect. Hence targeting GPCR heteromers constitutes an emerging strategy to select receptor-specific responses and is likely to be useful in achieving specific beneficial therapeutic effects.

Selective inhibition of glucose-stimulated insulin release by dantrolene

1982 ◽  
Vol 243 (1) ◽  
pp. E59-E67 ◽  
Author(s):  
D. Janjic ◽  
C. B. Wollheim ◽  
G. W. Sharp
Keyword(s):  
Insulin Release ◽  
Selective Inhibition ◽  
Calcium Stores ◽  
Dantrolene Sodium ◽  
Voltage Dependent ◽  
14Co2 Production ◽  
Stimulus Secretion Coupling ◽  
Primary Action ◽  
Ca2 Channels

Dantrolene sodium, which interferes with excitation-contraction coupling by inhibiting the Ca2+ release from sarcoplasmic reticulum in muscle, was used to investigate the role of stored calcium in the stimulation of insulin release by various secretagogues. Insulin release was measured simultaneously with 45Ca2+ uptake or 45Ca2+ efflux from isolated rat pancreatic islets. Glucose-stimulated insulin release was inhibited by dantrolene (10–100 microM) as was glyceraldehyde- or mannose-stimulated release. In contrast, dantrolene failed to inhibit insulin release stimulated by leucine, arginine, ouabain, potassium, or 3-isobutyl-1-methylxanthine. Although dantrolene lowered glucose-stimulated 45Ca2+ uptake, nonspecific blockade of voltage-dependent Ca2+ channels may not be a primary action of dantrolene because K+-stimulated 45Ca2+ uptake was not inhibited. Glucose utilization (3H2O formation) was unaffected by dantrolene, whereas glucose oxidation (14CO2 production) was decreased. In the absence of Ca2+, the glucose-inhibited 45Ca2+ efflux was unchanged. At normal Ca2+, dantrolene inhibited glucose-stimulated 45Ca2+ efflux and veratridine induced insulin release. This suggests an interference with mobilization of beta-cell calcium stores. The selective action of dantrolene on insulin release makes it an interesting tool for further studies on stimulus-secretion coupling.

Stimulation of prolactin release by dopamine withdrawal: role of calcium influx

1994 ◽  
Vol 267 (5) ◽  
pp. E789-E794 ◽  
Author(s):  
K. A. Gregerson ◽  
R. Chuknyiska ◽  
N. Golesorkhi
Keyword(s):  
Channel Blocker ◽  
Inositol Phosphates ◽  
Calcium Influx ◽  
Pituitary Cells ◽  
Induced Changes ◽  
Camp Levels ◽  
Ca2 Channels ◽  
Stimulation Of ◽  
Spiking Activity

Withdrawal of dopamine (DA), a neurotransmitter that inhibits prolactin (PRL) release from the anterior pituitary, stimulates PRL release with transient (30- to 45-min) secretory rates that exceed those observed before application of DA ("PRL rebound"). Using patch-clamp methods on identified rat lactotropes, we have demonstrated that a period of increased Ca(2+)-spiking activity follows recovery from the DA-induced hyperpolarization. The present experiments used dissociated pituitary cells to identify the relative roles of adenosine 3',5'-cyclic monophosphate (cAMP), inositol phosphates, and the enhanced influx of Ca2+ in the rebound secretion of PRL. Rebound secretion of PRL after DA withdrawal was completely blocked by the Ca2+ channel blocker verapamil (20 microM), which also inhibited spontaneous Ca(2+)-spiking activity. DA-induced changes in cAMP levels could be completely dissociated from the PRL rebound. Production of inositol phosphates rose after DA withdrawal but was secondary to the influx of Ca2+. These data demonstrate that influx of extracellular Ca2+ through verapamil-sensitive channels is a critical step in inducing PRL release after DA withdrawal. This finding supports our theory that DA-induced hyperpolarization recruits previously inactivated Ca2+ channels and upon DA washout the enhanced influx of Ca2+ through these voltage-regulated channels supports the rebound release of PRL.

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