scholarly journals Characteristics and Functions of α-Amino-3-Hydroxy-5-Methyl-4-Isoxazolepropionate Receptors Expressed in Mouse Pancreatic α-Cells

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1541-1550 ◽  
Author(s):  
Jung-Hwa Cho ◽  
Liangyi Chen ◽  
Mean-Hwan Kim ◽  
Robert H. Chow ◽  
Bertil Hille ◽  
...  
Keyword(s):  
Glutamate Receptor ◽  
Ampa Receptors ◽  
Islet Cells ◽  
Hormone Secretion ◽  
Cell Types ◽  
Membrane Depolarization ◽  
Voltage Gated ◽  
Mouse Pancreatic Islets ◽  
Inward Currents ◽  
Ca2 Channels

Pancreatic islet cells use neurotransmitters such as l-glutamate to regulate hormone secretion. We determined which cell types in mouse pancreatic islets express ionotropic glutamate receptor channels (iGluRs) and describe the detailed biophysical properties and physiological roles of these receptors. Currents through iGluRs and the resulting membrane depolarization were measured with patch-clamp methods. Ca2+ influx through voltage-gated Ca2+ channels and Ca2+-evoked exocytosis were detected by Ca2+ imaging and carbon-fiber microamperometry. Whereas iGluR2 glutamate receptor immunoreactivity was detected using specific antibodies in immunocytochemically identified mouse α- and β-cells, functional iGluRs were detected only in the α-cells. Fast application of l-glutamate to cells elicited rapidly activating and desensitizing inward currents at −60 mV. By functional criteria, the currents were identified as α-amino-3-hydroxy-5-methyl-4-isoxazolepropionate (AMPA) receptors. They were activated and desensitized by AMPA, and were activated only weakly by kainate. The desensitization by AMPA was inhibited by cyclothiazide, and the currents were blocked by 6-cyano-7-nitroquinoxaline-2,3-dione (CNQX). Islet iGluRs showed nonselective cation permeability with a low Ca2+ permeability (PCa/PNa = 0.16). Activation of the AMPA receptors induced a sequence of cellular actions in α-cells: 1) depolarization of the membrane by 27 ± 3 mV, 2) rise in intracellular Ca2+ mainly mediated by voltage-gated Ca2+ channels activated during the membrane depolarization, and 3) increase of exocytosis by the Ca2+ rise. In conclusion, iGluRs expressed in mouse α-cells resemble the low Ca2+-permeable AMPA receptor in brain and can stimulate exocytosis.

Ca2+ release from Ca2+ stores, particularly from ryanodine-sensitive Ca2+ stores, is required for the induction of LTD in cultured cerebellar Purkinje cells

1995 ◽  
Vol 74 (5) ◽  
pp. 2184-2188 ◽  
Author(s):  
K. Kohda ◽  
T. Inoue ◽  
K. Mikoshiba
Keyword(s):  
Purkinje Cells ◽  
Specific Inhibitor ◽  
Cell Voltage ◽  
Ruthenium Red ◽  
Mouse Embryos ◽  
Voltage Gated ◽  
Inward Currents ◽  
Cerebellar Purkinje Cells ◽  
Ca2 Channels

1. Primary-cultured cerebellar Purkinje cells (PCs) from mouse embryos were whole cell voltage clamped, and L-glutamate (Glu) was applied iontophoretically to the dendrite. Long-term depression (LTD) of Glu-evoked currents was induced through the conjunction of repeated depolarizations and Glu applications. 2. Thapsigargin, a specific inhibitor of Ca(2+)-ATPase on the endoplasmic reticulum, and ryanodine and ruthenium red, inhibitors of the ryanodine receptor, blocked the induction of LTD. 3. Thapsigargin and ryanodine alone did not affect influx of Ca2+ through voltage-gated Ca2+ channels and inward currents evoked by Glu applications. 4. Our results suggest that Ca2+ release from internal stores, particularly from ryanodine-sensitive stores, is necessary for the induction of LTD in cultured PCs.

scholarly journals Histones and basic polypeptides activate Ca2+/cation influx in various cell types

1998 ◽  
Vol 331 (2) ◽  
pp. 623-630 ◽  
Author(s):  
Alessandra GAMBERUCCI ◽  
Rosella FULCERI ◽  
Paola MARCOLONGO ◽  
William F. PRALONG ◽  
Angelo BENEDETTI
Keyword(s):  
Rat Hepatocytes ◽  
Cell Types ◽  
Membrane Depolarization ◽  
Histone H2a ◽  
Specific Manner ◽  
A Cell ◽  
Cell Depolarization ◽  
Influx Pathways ◽  
Basic Polypeptides ◽  
Ca2 Channels

Histone H2A (1–10 µg/ml) added to Ehrlich ascite cell suspensions promoted: (i) Ca2+ influx, but no apparent intracellular Ca2+ mobilization; (ii) plasma-membrane depolarization and Na+ influx in Ca2+-free medium, which were recovered by Ca2+ readmission; (iii) influx of other cations such as Ba2+, Mn2+, choline+ and N-methyl-d-glucamine+, but not of propidium+, ethidium bromide and Trypan Blue. H2A-induced Ca2+ influx and cell depolarization were: (i) blocked by La3+ and Gd3+, but not by various inhibitors of receptor-activated Ca2+-influx pathways/channels; (ii) mimicked by various basic polypeptides, with Mr > 4000; (iii) prevented or reversed by polyanions such as polyglutamate or heparin; (iv) present in other cell types, such as Jurkat, PC12 and Friend erythroleukaemia cells, but virtually absent from rat hepatocytes and thymocytes. We conclude that cationic proteins/polypeptides, by interacting in a cell-specific manner with the cell surface, can activate in those cells putative non-selective Ca2+ channels and membrane depolarization.

scholarly journals Role of transcription factors in the transdifferentiation of pancreatic islet cells

2015 ◽  
Vol 54 (2) ◽  
pp. R103-R117 ◽  
Author(s):  
Talitha van der Meulen ◽  
Mark O Huising
Keyword(s):  
Islet Cells ◽  
Hormone Secretion ◽  
Cell Types ◽  
Glucose Sensing ◽  
Glucose Disposal ◽  
Pancreatic Islet Cells ◽  
Β Cells ◽  
Transcription Factor Networks ◽  
Low Levels

The α and β cells act in concert to maintain blood glucose. The α cells release glucagon in response to low levels of glucose to stimulate glycogenolysis in the liver. In contrast, β cells release insulin in response to elevated levels of glucose to stimulate peripheral glucose disposal. Despite these opposing roles in glucose homeostasis, α and β cells are derived from a common progenitor and share many proteins important for glucose sensing and hormone secretion. Results from recent work have underlined these similarities between the two cell types by revealing that β-to-α as well as α-to-β transdifferentiation can take place under certain experimental circumstances. These exciting findings highlight unexpected plasticity of adult islets and offer hope of novel therapeutic paths to replenish β cells in diabetes. In this review, we focus on the transcription factor networks that establish and maintain pancreatic endocrine cell identity and how they may be perturbed to facilitate transdifferentiation.

scholarly journals STIM Proteins and Glutamate Receptors in Neurons: Role in Neuronal Physiology and Neurodegenerative Diseases

2019 ◽  
Vol 20 (9) ◽  
pp. 2289 ◽  
Author(s):  
Karolina Serwach ◽  
Joanna Gruszczynska-Biegala
Keyword(s):  
Traumatic Brain Injury ◽  
Neurodegenerative Diseases ◽  
Glutamate Receptors ◽  
Glutamate Receptor ◽  
Neurodegenerative Disorders ◽  
Present Evidence ◽  
Voltage Gated ◽  
Pathological Conditions ◽  
Neuronal Physiology ◽  
Ca2 Channels

Neuronal calcium (Ca2+) influx has long been ascribed mainly to voltage-gated Ca2+ channels and glutamate receptor channels. Recent research has shown that it is also complemented by stromal interaction molecule (STIM) protein-mediated store-operated Ca2+ entry (SOCE). SOCE is described as Ca2+ flow into cells in response to the depletion of endoplasmic reticulum Ca2+ stores. The present review summarizes recent studies that indicate a relationship between neuronal SOCE that is mediated by STIM1 and STIM2 proteins and glutamate receptors under both physiological and pathological conditions, such as neurodegenerative disorders. We present evidence that the dysregulation of neuronal SOCE and glutamate receptor activity are hallmarks of acute neurodegenerative diseases (e.g., traumatic brain injury and cerebral ischemia) and chronic neurodegenerative diseases (e.g., Alzheimer’s disease and Huntington’s disease). Emerging evidence indicates a role for STIM proteins and glutamate receptors in neuronal physiology and pathology, making them potential therapeutic targets.

Ionic currents and endothelin signaling in smooth muscle cells from rat renal resistance arteries

1994 ◽  
Vol 266 (2) ◽  
pp. F325-F341 ◽  
Author(s):  
D. V. Gordienko ◽  
C. Clausen ◽  
M. S. Goligorsky
Keyword(s):  
Smooth Muscle ◽  
Smooth Muscle Cells ◽  
Reversal Potential ◽  
Muscle Cells ◽  
Membrane Depolarization ◽  
Disulfonic Acid ◽  
Patch Clamp Technique ◽  
Voltage Range ◽  
Voltage Gated ◽  
Ca2 Channels

The repertoire of ionic channels expressed in myocytes freshly isolated from microdissected interlobar and arcuate arteries of rat kidney and their integrative behavior in response to endothelin-1 (ET-1) were studied by identification and characterization of major whole cell current components using patch-clamp technique. In renal microvascular smooth muscle cells (RMSMC) dialyzed with K(+)-containing solution, rapidly inactivating (Ito) and sustained outward K+ currents were identified. Voltage-dependent Ito was categorized as "A" current based on its kinetics, sensitivity to 4-aminopyridine (4-AP), and refractoriness to tetraethylammonium (TEA+). Ca(2+)-activated component of K+ current was completely blocked by 10 mM TEA+, whereas 5 mM 4-AP did not affect this current. Maximal Ca2+ current (ICa) recorded in Cs(+)-loaded RMSMC reached 250 pA when cells were bathed in a solution with 2.5 mM Ca2+. Two patterns of ICa differing in kinetics, voltage range of activation and inactivation, and sensitivity to nifedipine were identified as T and L currents. Ca(2+)-dependent current component showing reversal potential near Cl- current (ECl) and sensitivity to blocking action of 4,4'-diisothiocyanostilbene-2,2'-disulfonic acid was identified as Ca(2+)-activated ECl. Activation of RMSMC with ET-1 (1-10 nM) induced elevation of [Ca2+]i and subsequent activation of Ca(2+)-activated ICl, which led to membrane depolarization sufficient to activate voltage-gated Ca2+ channels. ET-1-evoked transient reduction of ICa carried through voltage-gated Ca2+ channels was followed by augmentation of L-type ICa. ET-1-induced mobilization of intracellular Ca2+, accompanied by membrane depolarization, resulted in activation of Ca(2+)-dependent K+ channels, which can play the role of a feedback element terminating ET-1-induced membrane depolarization.

The imidazoline derivative calmidazolium inhibits voltage-gated Ca2+-channels and insulin release but has no effect on the phospholipase C system in insulin producing RINm5F-cells

1994 ◽  
Vol 14 (3) ◽  
pp. 145-158 ◽  
Author(s):  
Henrik Kindmark ◽  
Martin Köhler ◽  
Pär Gerwins ◽  
Olof Larsson ◽  
Akhtar Khan ◽  
...  
Keyword(s):  
Insulin Release ◽  
Hormone Secretion ◽  
Rinm5f Cells ◽  
Calmodulin Antagonist ◽  
Voltage Gated ◽  
Mechanism Of Inhibition ◽  
Dependent Protein ◽  
Direct Binding ◽  
Ca2 Channels ◽  
Imidazoline Derivative

The present study shows that the calmodulin antagonist calmidazolium inhibited influx of Ca2+ through voltage-gated Ca2+-channels in clonal insulin producing RINm5F-cells. The mechanism of inhibition may involve both Ca2+-calmodulin-dependent protein kinases and direct binding of calmidazolium to the Ca2+-channel. Calmidazolium did not affect uptake of Ca2+ into intracellular Ca2+-pools, inositol 1,4,5-trisphosphate (InsP3) formation or action on intracellular Ca2+-pools. The calmodulin inhibitor also did not affect glucose utilization or oxidation in RINm5F-cells, speaking against an unspecific toxic effect of the compound. KCl-and ATP-stimulated insulin release from RINm5F-cells was attenuated by calmidazolium, whereas basal hormone secretion was unaffected.

Effect of Ca2+ and cAMP on capacitance-measured hormone secretion in human GH-secreting adenoma cells

1998 ◽  
Vol 275 (4) ◽  
pp. E649-E654 ◽  
Author(s):  
Tsukasa Takei ◽  
Junko Yasufuku-Takano ◽  
Koji Takano ◽  
Toshiro Fujita ◽  
Naohide Yamashita
Keyword(s):  
Growth Hormone ◽  
Hormone Secretion ◽  
Human Growth ◽  
Membrane Depolarization ◽  
Intracellular Camp ◽  
Growth Hormone Releasing Hormone ◽  
Patch Clamp Technique ◽  
Releasing Hormone ◽  
Voltage Gated ◽  
Whole Cell Patch Clamp

Membrane capacitance ( C m) was measured as an index of exocytosis in human growth hormone-secreting adenoma cells using the perforated whole cell, patch-clamp technique; the effects of membrane depolarization, growth hormone-releasing hormone, and 8-bromoadenosine 3′,5′-cyclic monophosphate (8-BrcAMP) were examined. C m was increased by membrane depolarization to potentials beyond the threshold necessary to open voltage-gated Ca2+channels. These voltage-dependent changes in C m varied as a function of both depolarization amplitude and duration and were blocked in the presence of the Ca2+channel antagonist nitrendipine (10−6 M). When membrane potential was clamped at the holding potential (−78 mV), voltage-gated Ca2+ channels were closed, and neither application of growth hormone-releasing hormone nor 8-BrcAMP affected C m. However, when these agents were applied to depolarized cells, where the voltage-gated Ca2+ channels were open, the increases in C mwere augmented. From these data, it was concluded that elevation of intracellular cAMP, per se, did not stimulate exocytosis. Rather, Ca2+ influx through voltage-gated channels was a prerequisite for cAMP-induced exocytosis.

Roles of Ca2+ influx through ATP-activated channels in catecholamine release from pheochromocytoma PC12 cells

1992 ◽  
Vol 68 (6) ◽  
pp. 2026-2032 ◽  
Author(s):  
K. Nakazawa ◽  
K. Inoue
Keyword(s):  
Pc12 Cells ◽  
Dopamine Release ◽  
Cell Voltage ◽  
Catecholamine Release ◽  
K Channel ◽  
Voltage Gated ◽  
Inward Currents ◽  
Pheochromocytoma Pc12 ◽  
Pheochromocytoma Pc12 Cells ◽  
Ca2 Channels

1. Extracellular ATP evokes catecholamine release concomitant with depolarization in pheochromocytoma PC12 cells. Roles of Ca2+ influx through ATP-activated channels during the catecholamine release were investigated. 2. Norepinephrine or dopamine release induced by > or = 100-microM concentrations of ATP was insensitive to 300 microM Cd2+, whereas the release induced by increasing extracellular KCl (50-150 mM) was completely blocked by this concentration of Cd2+. 3. ATP (100 microM) increased the intracellular free Ca2+ concentration measured with fura-2. The increase was not affected by 300 microM Cd2+ or 100 microM nicardipine, suggesting that Ca2+ influx through ATP-activated channels but not through voltage-gated Ca2+ channels contributes to the ATP-evoked catecholamine release. 4. Inward currents permeating through voltage-gated Ca2+ channels were measured using the whole-cell voltage clamp. In the presence of 10 microM ATP, a concentration that induces an ATP-activated channel-mediated current equivalent to that induced by 100 microM ATP during the depolarization in "non-voltage clamped" cells, the Ca2+ current activated by a voltage step to +10 mV was reduced. The reduction in the Ca2+ channel-mediated current was not observed when the extracellular Ca2+ was replaced with Ba2+. 5. The ATP (100 microM)-evoked dopamine release was inhibited by 300 microM Cd2+ when measured with extracellular Ba2+ instead of Ca2+. This effect of Ba2+ may not be related to K+ channel-blocking activity, because the ATP-evoked dopamine release obtained with 5 mM tetraethylammonium (TEA) was not inhibited by Cd2+.(ABSTRACT TRUNCATED AT 250 WORDS)

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