scholarly journals Muscarinic stimulation exerts both stimulatory and inhibitory effects on the concentration of cytoplasmic Ca2+ in the electrically excitable pancreatic B-cell

1995 ◽  
Vol 311 (1) ◽  
pp. 259-267 ◽  
Author(s):  
P Gilon ◽  
M Nenquin ◽  
J C Henquin
Keyword(s):  
Steady State ◽  
B Cells ◽  
Second Phase ◽  
Inhibitory Effects ◽  
Muscarinic Stimulation ◽  
Voltage Dependent ◽  
Mouse Pancreatic Islets ◽  
Pancreatic B Cells ◽  
High Concentrations ◽  
Ca2 Channels

Mouse pancreatic islets were used to investigate how muscarinic stimulation influences the cytoplasmic Ca2+ concentration ([Ca2+]i) in insulin-secreting B-cells. In the absence of extracellular Ca2+, acetylcholine (ACh) triggered a transient, concentration-dependent and thapsigargin-inhibited increase in [Ca2+]i. In the presence of extracellular Ca2+ and 15 mM glucose, ACh induced a biphasic rise in [Ca2+]i. The initial, transient phase increased with the concentration of ACh, whereas the second, sustained, phase was higher at low (0.1-1 microM) than at high (> or = 10 microM) concentrations of ACh. Thapsigargin attenuated (did not suppress) the first phase of the [Ca2+]i rise and did not affect the sustained response. This sustained rise was inhibited by omission of extracellular Na+ (which prevents the depolarizing action of ACh) and by D600 or diazoxide (which prevent activation of voltage-dependent Ca2+ channels). During steady-state stimulation, the Ca2+ action potentials in B-cells were stimulated by 1 microM ACh but inhibited by 100 microM ACh. When B-cells were depolarized by 45 mM K+, ACh induced a concentration-dependent, biphasic change in [Ca2+]i, consisting of a first peak rapidly followed by a decrease. Thapsigargin suppressed the peak without affecting the drop in [Ca2+]i. Measurements of 45Ca2+ efflux under similar conditions indicated that ACh decreases Ca2+ influx and slightly increases the efflux. All effects of ACh were blocked by atropine. In conclusion, three mechanisms at least are involved in the biphasic change in [Ca2+]i that muscarinic stimulation exerts in excitable pancreatic B-cells. A mobilization of Ca2+ from the endoplasmic reticulum contributes significantly to the first peak, but little to the steady-state rise in [Ca2+]i. This second phase results from an influx of Ca2+ through voltage-dependent Ca2+ channels activated by a Na(+)-dependent depolarization. However, when high concentrations of ACh are used, Ca2+ influx is attenuated.

No evidence for a role of reverse Na(+)-Ca2+ exchange in insulin release from mouse pancreatic islets

1996 ◽  
Vol 271 (3) ◽  
pp. E426-E433
Author(s):  
M. J. Garcia-Barrado ◽  
P. Gilon ◽  
Y. Sato ◽  
M. Nenquin ◽  
J. C. Henquin
Keyword(s):  
Membrane Potential ◽  
B Cells ◽  
Electrical Activity ◽  
Insulin Release ◽  
Voltage Dependent ◽  
Small Rise ◽  
Mouse Pancreatic Islets ◽  
Mouse Islets ◽  
Ca2 Channels

We studied whether reverse Na(+)-Ca2+ exchange can increase cytoplasmic Ca2+ ([Ca2+]i) in mouse islets and contribute to insulin release. The exchange was stimulated by replacing Na+ with choline, sucrose, or lithium in a medium containing 15 mM glucose. Na+ omission increased electrical activity in B cells, [Ca2+]i, and insulin release. When voltage-dependent Ca2+ channels were blocked by nimodipine or closed by holding the membrane polarized with diazoxide, Na+ omission caused a slight hyperpolarization, a small rise in [Ca2+]i, and a marginal increase in insulin release (the latter only with choline). This small rise in [Ca2+]i was dependent on extracellular Ca2+ but was hardly augmented when intracellular Na+ was raised with alanine. When B cells were depolarized by 30 mM K+, Na+ omission did not affect the membrane potential but increased [Ca2+]i and insulin release. If Ca2+ channels were blocked by nimodipine, only marginal increases in Ca2+ and insulin release persisted, which were not different from those observed when the cells were not depolarized. This indicates that Ca2+ influx through voltage-dependent Ca2+ channels rather than via reverse Na(+)-Ca2+ exchange underlies the rise in [Ca2+]i and in insulin release produced by Na+ removal. No decisive support for Ca2+ influx by reverse Na(+)-Ca2+ exchange could be found.

scholarly journals Calcium efflux and cycling across the synaptosomal plasma membrane

1985 ◽  
Vol 226 (1) ◽  
pp. 225-231 ◽  
Author(s):  
R Snelling ◽  
D Nicholls
Keyword(s):  
Plasma Membrane ◽  
Steady State ◽  
Potential Gradient ◽  
Electrochemical Potential ◽  
Electrochemical Gradient ◽  
Calcium Efflux ◽  
Normal Medium ◽  
Voltage Dependent ◽  
Synaptosomal Plasma Membrane ◽  
Ca2 Channels

Ca2+ efflux from intact synaptosomes is investigated. Net efflux can be induced by returning synaptosomes from media with elevated Ca2+ or high pH to a normal medium. Net Ca2+ efflux is accelerated when the Na+ electrochemical potential gradient is collapsed by veratridine plus ouabain. Under steady-state conditions at 30 degrees C, Ca2+ cycles across the plasma membrane at 0.38 nmol . min-1 . mg-1 of protein. Exchange is increased by 145% by veratridine plus ouabain, both influx and efflux being increased. Increased influx is probably due to activation of voltage-dependent Ca2+ channels, since it is abolished by verapamil. The results indicate that, at least under conditions of low Na+ electrochemical gradient, some pathway other than a Na+/Ca2+ exchange must operate in the plasma membrane to expel Ca2+.

Ca(2+)-induced inhibition of 45Ca2+ influx and Ca2+ current in smooth muscle of the rat vas deferens

1996 ◽  
Vol 270 (5) ◽  
pp. C1468-C1477 ◽  
Author(s):  
M. A. Khoyi ◽  
T. Ishikawa ◽  
K. D. Keef ◽  
D. P. Westfall
Keyword(s):  
Vas Deferens ◽  
Rat Vas Deferens ◽  
Inhibitory Effects ◽  
Isolated Cells ◽  
Inositol 1,4,5 Trisphosphate ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Inward Currents ◽  
K Concentration ◽  
Ca2 Channels

The present study investigates how changes in intracellular Ca2+ concentration modulate the influx of 45Ca2+ in isolated rat vasa deferentia. Raising extracellular K+ concentration ([K+]0) to > or = 32 mM increased 45Ca2+ influx during the 1st min in solutions containing 0.03-1.5 mM extracellular Ca2+ concentration ([Ca2+]0). During the 6th min in [K+]0 > or = 50 mM, 45Ca2+ influx was less than during the 1st min. This decline in 45Ca2+ influx occurred for [Ca2+]0 > or = 0.4 mM. Procaine potentiated K(+)-stimulated 45Ca2+ influx in 1.5 mM [Ca2+]0 and eliminated the decline of 45Ca2+ influx in low [Ca2-]0. Ryanodine and norepinephrine reduced K(+)-stimulated 45Ca2+ influx. 45Ca2+ content changed with time in accordance with the changes observed in 45Ca2+ influx. In isolated cells, voltage-dependent inward currents inactivated more rapidly with 1.5 mM Ca2+ as the charge carrier than with 1.5 mM Ba2+, and the steady-state inactivation relationship was shifted in the hyperpolarizing direction. Inward current was reduced with either caffeine, ryanodine, or norepinephrine. The inhibitory effects of norepinephrine were abolished by depletion of intracellular Ca2+ stores. These results are compatible with the hypothesis that K(+)-stimulated 45Ca2+ influx declines with time due to Ca(2+)-induced inhibition of Ca2- channels. Ca(2+)- and inositol 1,4,5-trisphosphate-induced releases of Ca2+ from the sarcoplasmic reticulum appear to play an important role in this process.

scholarly journals Voltage-dependent inactivation of slow calcium channels in intact twitch muscle fibers of the frog.

1989 ◽  
Vol 94 (5) ◽  
pp. 937-951 ◽  
Author(s):  
G Cota ◽  
E Stefani
Keyword(s):  
Steady State ◽  
Rate Constant ◽  
Voltage Dependence ◽  
Muscle Fibers ◽  
Dependent Manner ◽  
Inactivation Curve ◽  
Voltage Dependent ◽  
Steady State Inactivation ◽  
Intact Muscle ◽  
Ca2 Channels

Inactivation of slow Ca2+ channels was studied in intact twitch skeletal muscle fibers of the frog by using the three-microelectrode voltage-clamp technique. Hypertonic sucrose solutions were used to abolish contraction. The rate constant of decay of the slow Ca2+ current (ICa) remained practically unchanged when the recording solution containing 10 mM Ca2+ was replaced by a Ca2+-buffered solution (126 mM Ca-maleate). The rate constant of decay of ICa monotonically increased with depolarization although the corresponding time integral of ICa followed a bell-shaped function. The replacement of Ca2+ by Ba2+ did not result in a slowing of the rate of decay of the inward current nor did it reduce the degree of steady-state inactivation. The voltage dependence of the steady-state inactivation curve was steeper in the presence of Ba2+. In two-pulse experiments with large conditioning depolarizations ICa inactivation remained unchanged although Ca2+ influx during the prepulse greatly decreased. Dantrolene (12 microM) increased mechanical threshold at all pulse durations tested, the effect being more prominent for short pulses. Dantrolene did not significantly modify ICa decay and the voltage dependence of inactivation. These results indicate that in intact muscle fibers Ca2+ channels inactivate in a voltage-dependent manner through a mechanism that does not require Ca2+ entry into the cell.

scholarly journals Fast Exocytosis with Few Ca2+ Channels in Insulin-Secreting Mouse Pancreatic B Cells

2001 ◽  
Vol 81 (6) ◽  
pp. 3308-3323 ◽  
Author(s):  
Sebastian Barg ◽  
Xiaosong Ma ◽  
Lena Eliasson ◽  
Juris Galvanovskis ◽  
Sven O. Göpel ◽  
...  
Keyword(s):  
B Cells ◽  
Pancreatic B Cells ◽  
Ca2 Channels

In Vitro Effects of Ethanol on Rabbit Platelet Aggregation, Secretion of Granule Contents, and Cyclic AMP Levels in the Presence of Prostacyclin

1989 ◽  
Vol 61 (02) ◽  
pp. 254-258 ◽  
Author(s):  
Margaret L Rand ◽  
Peter L Gross ◽  
Donna M Jakowec ◽  
Marian A Packham ◽  
J Fraser Mustard
Keyword(s):  
Cyclic Amp ◽  
Inhibitory Effect ◽  
Rabbit Platelet ◽  
Inhibitory Effects ◽  
Low Concentrations ◽  
Rabbit Platelets ◽  
High Concentrations ◽  
In Vitro Effects ◽  
Aggregation Of Platelets

SummaryEthanol, at physiologically tolerable concentrations, inhibits platelet responses to low concentrations of collagen or thrombin, but does not inhibit responses of washed rabbit platelets stimulated with high concentrations of ADP, collagen, or thrombin. However, when platelet responses to high concentrations of collagen or thrombin had been partially inhibited by prostacyclin (PGI2), ethanol had additional inhibitory effects on aggregation and secretion. These effects were also observed with aspirin- treated platelets stimulated with thrombin. Ethanol had no further inhibitory effect on aggregation of platelets stimulated with ADP, or the combination of ADP and epinephrine. Thus, the inhibitory effects of ethanol on platelet responses in the presence of PGI2 were very similar to its inhibitory effects in the absence of PGI2, when platelets were stimulated with lower concentrations of collagen or thrombin. Ethanol did not appear to exert its inhibitory effects by increasing cyclic AMP above basal levels and the additional inhibitory effects of ethanol in the presence of PGI2 did not appear to be brought about by further increases in platelet cyclic AMP levels.

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