scholarly journals Effects of caffeine on cytoplasmic free Ca2+ concentration in pancreatic β-cells are mediated by interaction with ATP-sensitive K+ channels and L-type voltage-gated Ca2+ channels but not the ryanodine receptor

1995 ◽  
Vol 306 (3) ◽  
pp. 679-686 ◽  
Author(s):  
M S Islam ◽  
O Larsson ◽  
T Nilsson ◽  
P O Berggren
Keyword(s):  
Cyclic Amp ◽  
Beta Cells ◽  
Insulin Release ◽  
Ryanodine Receptor ◽  
Katp Channel ◽  
Channel Activity ◽  
K Channels ◽  
Voltage Gated ◽  
Induced Changes ◽  
Ca2 Channels

In the pancreatic beta-cell, an increase in the cytoplasmic free Ca2+ concentration ([Ca2+]i) by caffeine is believed to indicate mobilization of Ca2+ from intracellular stores, through activation of a ryanodine receptor-like channel. It is not known whether other mechanisms, as well, underlie caffeine-induced changes in [Ca2+]i. We studied the effects of caffeine on [Ca2+]i by using dual-wavelength excitation microfluorimetry in fura-2-loaded beta-cells. In the presence of a non-stimulatory concentration of glucose, caffeine (10-50 mM) consistently increased [Ca2+]i. The effect was completely blocked by omission of extracellular Ca2+ and by blockers of the L-type voltage-gated Ca2+ channel, such as D-600 or nifedipine. Depletion of agonist-sensitive intracellular Ca2+ pools by thapsigargin did not inhibit the stimulatory effect of caffeine on [Ca2+]i. Moreover, this effect of caffeine was not due to an increase in cyclic AMP, since forskolin and 3-isobutyl-1-methylxanthine (IBMX) failed to raise [Ca2+]i in unstimulated beta-cells. In beta-cells, glucose and sulphonylureas increase [Ca2+]i by causing closure of ATP-sensitive K+ channels (KATP channels). Caffeine also caused inhibition of KATP channel activity, as measured in excised inside-out patches. Accordingly, caffeine (> 10 mM) induced insulin release from beta-cells in the presence of a non-stimulatory concentration of glucose (3 mM). Hence, membrane depolarization and opening of voltage-gated L-type Ca2+ channels were the underlying mechanisms whereby the xanthine drug increased [Ca2+]i and induced insulin release. Paradoxically, in glucose-stimulated beta-cells, caffeine (> 10 mM) lowered [Ca2+]i. This effect was due to the fact that caffeine reduced depolarization-induced whole-cell Ca2+ current through the L-type voltage-gated Ca2+ channel in a dose-dependent manner. Lower concentrations of caffeine (2.5-5.0 mM), when added after glucose-stimulated increase in [Ca2+]i, induced fast oscillations in [Ca2+]i. The latter effect was likely to be attributable to the cyclic AMP-elevating action of caffeine, leading to phosphorylation of voltage-gated Ca2+ channels. Hence, in beta-cells, caffeine-induced changes in [Ca2+]i are not due to any interaction with intracellular Ca2+ pools. In these cells, a direct interference with KATP channel- and L-type voltage-gated Ca(2+)-channel activity is the underlying mechanism by which caffeine increases or decreases [Ca2+]i.

scholarly journals Nitric oxide opens ATP-sensitive K+ channels through suppression of phosphofructokinase activity and inhibits glucose-induced insulin release in pancreatic beta cells.

1994 ◽  
Vol 104 (6) ◽  
pp. 1079-1098 ◽  
Author(s):  
Y Tsuura ◽  
H Ishida ◽  
S Hayashi ◽  
K Sakamoto ◽  
M Horie ◽  
...  
Keyword(s):  
Nitric Oxide ◽  
Insulin Secretion ◽  
Beta Cells ◽  
Katp Channel ◽  
Pancreatic Beta Cells ◽  
Katp Channels ◽  
Channel Activity ◽  
K Channels ◽  
Intracellular Mechanism ◽  
Phosphofructokinase Activity

Nitric oxide (NO) is known to be a potent messenger in the intracellular signal transduction system in many tissues. In pancreatic beta cells, NO has been reported to be formed from L-arginine through NO synthase. To elucidate the effect of NO on insulin secretion and to investigate the intracellular mechanism of its effect, we have used sodium nitroprusside (SNP) as a NO donor. SNP inhibited glucose-induced insulin secretion in a dose-dependent manner, and its effect was reversed by hemoglobin, a known NO scavenger. However, glyceraldehyde-induced insulin secretion was not affected by SNP. Since the closure of ATP-sensitive K+ channels (KATP channel) has been established as a key step in glucose-induced insulin secretion, we have directly assessed the effect of SNP on KATP channel activity using the patch clamp technique. The KATP channel activity reduced by glucose was found to be reversibly activated by the addition of SNP, and this activation was able to be similarly reproduced by applying S-Nitroso-N-acetyl-DL-penicillamine (SNAP), another NO generator. Furthermore, these activating effects were completely eliminated by hemoglobin, in accordance with the reversibility in inhibition of glucose-induced insulin release. However, SNP could not affect the KATP channel suppression by ATP applied to the inside of the plasma membrane. The activation of the KATP channel by NO, therefore, seems to be due to the decreased ATP production attributable to impairment of glucose metabolism in beta cells. Since SNP exhibited no effect on glyceraldehyde-induced KATP channel inhibition, NO may disturb a glycolytic step before glyceraldehyde-3-phosphate. The KATP channel activation by 2-deoxyglucose through presumable ATP consumption due to its phosphorylation by glucokinase was, however, not affected even in the presence of SNP. But in the permeabilized beta cells made by exposure to a low concentration (0.02 U/ml) of streptolysin O (open cell-attached configuration), SNP reopens KATP channels which have been eliminated by fructose-6-phosphate, while this effect was not observed in the KATP channels inhibited by fructose-1,6-bisphosphate. On the other hand, in rat ventricular myocyte KATP channels were not activated by SNP even under a low concentration of glucose. From these observations, the inhibition of phosphofructokinase activity is probably the site responsible for the impairment of glucose metabolism induced by NO in pancreatic beta cells. NO, therefore, seems to be a factor in the deterioration of glucose-induced insulin secretion from pancreatic beta cells through a unique intracellular mechanism.

Enhancement of Voltage-Gated K+ Channels and Depression of Voltage-Gated Ca2+ Channels Are Involved in Quercetin-Induced Vasorelaxation in Rat Coronary Artery

Planta Medica ◽  
2014 ◽  
Vol 80 (06) ◽  
pp. 465-472 ◽  
Author(s):  
Xiaomin Hou ◽  
Yu Liu ◽  
Longgang Niu ◽  
Lijuan Cui ◽  
Mingsheng Zhang
Keyword(s):  
Coronary Artery ◽  
K Channels ◽  
Voltage Gated ◽  
Ca2 Channels

scholarly journals Activation of pre-synaptic M-type K+channels inhibits [3H]d-aspartate release by reducing Ca2+entry through P/Q-type voltage-gated Ca2+channels

2009 ◽  
Vol 109 (1) ◽  
pp. 168-181 ◽  
Author(s):  
Rosa Luisi ◽  
Elisabetta Panza ◽  
Vincenzo Barrese ◽  
Fabio Arturo Iannotti ◽  
Davide Viggiano ◽  
...  
Keyword(s):  
K Channels ◽  
Voltage Gated ◽  
Type K ◽  
Ca2 Channels

Development of the biphasic response to glucose in fetal and neonatal rat pancreas

1988 ◽  
Vol 254 (2) ◽  
pp. E167-E174 ◽  
Author(s):  
R. L. Hole ◽  
M. C. Pian-Smith ◽  
G. W. Sharp
Keyword(s):  
Beta Cell ◽  
Insulin Release ◽  
Neonatal Rat ◽  
Biphasic Response ◽  
Rat Pancreas ◽  
K Channels ◽  
Fetal Pancreas ◽  
Biphasic Insulin ◽  
Biphasic Insulin Release ◽  
Ca2 Channels

A study on the development of biphasic insulin release and sensitivity to inhibitors has been performed using perifused rat pancreas at 19.5 days of gestation (3 days before birth) and at 3 days after birth. In the fetal pancreas, 16.7 mM glucose caused a marked stimulation of insulin release that did not, however, manifest a biphasic response and was not inhibited by verapamil, a Ca2+ channel blocker. This suggested that the immature response was due to either a lack of voltage-dependent Ca2+ channels or their failure to open in response to glucose. Depolarizing concentrations of KCl stimulated insulin release, which was inhibited by verapamil, demonstrating that functional Ca2+ channels were present. In the presence of 16.7 mM glucose, quinine, which blocks glucose-sensitive k+ channels, potentiated the response of the fetal pancreas that now became sensitive to verapamil, demonstrating that functional K+ channels were also present in the fetal pancreatic beta-cell. The immaturity of the response is not due specifically to a defect in glucose metabolism; rather the metabolism of nutrient secretagogues fails to couple with the K+ channel in the fetal islet and thus fails to depolarize the beta-cell membrane. Three days after birth the pattern of response to high glucose is biphasic. Insulin release in fetal pancreas was inhibited by epinephrine and somatostatin.

scholarly journals Disturbances in Glucose-Tolerance, Insulin-Release, and Stress-Induced Hyperglycemia upon Disruption of the Cav2.3 (α1E) Subunit of Voltage-Gated Ca2+Channels

2002 ◽  
Vol 16 (4) ◽  
pp. 884-895 ◽  
Author(s):  
Alexey Pereverzev ◽  
Marina Mikhna ◽  
Rolf Vajna ◽  
Cornelia Gissel ◽  
Margit Henry ◽  
...  
Keyword(s):  
Glucose Tolerance ◽  
Insulin Release ◽  
Voltage Gated ◽  
Ca2 Channels

scholarly journals Role of pertussis toxin-sensitive G-protein, K+ channels, and voltage-gated Ca2+ channels in the antinociceptive effect of inosine

2012 ◽  
Vol 9 (1) ◽  
pp. 51-58 ◽  
Author(s):  
Sérgio José Macedo-Junior ◽  
Francisney Pinto Nascimento ◽  
Murilo Luiz-Cerutti ◽  
Adair Roberto Soares Santos
Keyword(s):  
G Protein ◽  
Pertussis Toxin ◽  
Antinociceptive Effect ◽  
K Channels ◽  
Voltage Gated ◽  
Ca2 Channels

scholarly journals Activity-dependent regulation of T-type calcium channels by submembrane calcium ions

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Magali Cazade ◽  
Isabelle Bidaud ◽  
Philippe Lory ◽  
Jean Chemin
Keyword(s):  
Calcium Ions ◽  
Large Decrease ◽  
Channel Activity ◽  
Ionotropic Receptors ◽  
Voltage Gated ◽  
Dependent Inactivation ◽  
Steady State Inactivation ◽  
Activity Dependent ◽  
Hyperpolarizing Shift ◽  
Ca2 Channels

Voltage-gated Ca2+ channels are involved in numerous physiological functions and various mechanisms finely tune their activity, including the Ca2+ ion itself. This is well exemplified by the Ca2+-dependent inactivation of L-type Ca2+ channels, whose alteration contributes to the dramatic disease Timothy Syndrome. For T-type Ca2+ channels, a long-held view is that they are not regulated by intracellular Ca2+. Here we challenge this notion by using dedicated electrophysiological protocols on both native and expressed T-type Ca2+ channels. We demonstrate that a rise in submembrane Ca2+ induces a large decrease in T-type current amplitude due to a hyperpolarizing shift in the steady-state inactivation. Activation of most representative Ca2+-permeable ionotropic receptors similarly regulate T-type current properties. Altogether, our data clearly establish that Ca2+ entry exerts a feedback control on T-type channel activity, by modulating the channel availability, a mechanism that critically links cellular properties of T-type Ca2+ channels to their physiological roles.

scholarly journals Mitogen-induced changes in Ca2+ permeability are not mediated by voltage-gated K+ channels.

1986 ◽  
Vol 261 (25) ◽  
pp. 11520-11523 ◽  
Author(s):  
E W Gelfand ◽  
R K Cheung ◽  
S Grinstein
Keyword(s):  
K Channels ◽  
Voltage Gated ◽  
Induced Changes
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