scholarly journals Choline and NMDG directly reduce outward currents: reduced outward current when these substances replace Na+ is alone not evidence of Na+-activated K+ currents

2018 ◽  
Vol 120 (6) ◽  
pp. 3217-3233 ◽  
Author(s):  
Jeffrey B. Thuma ◽  
Scott L. Hooper
Keyword(s):  
Sodium Chloride ◽  
Potassium Channels ◽  
Normal Saline ◽  
Choline Chloride ◽  
Outward Current ◽  
Sodium Concentration ◽  
Outward Currents ◽  
High Concentrations ◽  
Retzius Cells ◽  
Extracellular Sodium

Choline chloride is often, and N-methyl-d-glucamine (NMDG) sometimes, used to replace sodium chloride in studies of sodium-activated potassium channels. Given the high concentrations used in sodium replacement protocols, it is essential to test that it is not the replacement substances themselves, as opposed to the lack of sodium, that cause any observed effects. We therefore compared, in lobster stomatogastric neurons and leech Retzius cells, the effects of applying salines in which choline chloride replaced sodium chloride, and in which choline hydroxide or sucrose was added to normal saline. We also tested, in stomatogastric neurons, the effect of adding NMDG to normal saline. These protocols allowed us to measure the direct effects (i.e., effects not due to changes in sodium concentration or saline osmolarity or ionic strength) of choline on stomatogastric and leech currents, and of NMDG on stomatogastric currents. Choline directly reduced transient and sustained depolarization-activated outward currents in both species, and NMDG directly reduced transient depolarization-activated outward currents in stomatogastric neurons. Experiments with lower choline concentrations showed that adding as little as 150 mM (stomatogastric) or 5 mM (leech) choline reduced at least some depolarization-activated outward currents. Reductions in outward current with choline chloride or NMDG replacement alone are thus not evidence of sodium-activated potassium currents. NEW & NOTEWORTHY We show that choline or N-methyl-d-glucamine (NMDG) directly (i.e., not due to changes in extracellular sodium) decrease outward currents. Prior work studying sodium-activated potassium channels in which sodium was replaced with choline or NMDG without an addition control may therefore be artifactual.

scholarly journals The Effect of Glycerol Treatment of Voltage-Clamped Snake Muscle Fibers

1973 ◽  
Vol 61 (2) ◽  
pp. 176-184 ◽  
Author(s):  
Hiroshi Washio
Keyword(s):  
Normal Saline ◽  
Surface Membrane ◽  
Muscle Fibers ◽  
Outward Current ◽  
Tension Development ◽  
Normal Medium ◽  
Outward Currents ◽  
Delayed Rectification ◽  
Glycerol Treatment ◽  
Contractile Activation

The effect of glycerol treatment on the membrane currents and tension development was studied in voltage clamped snake muscle fibers. In muscle fibers which were exposed for 1 h to a normal saline containing 400 mM glycerol and then returned to a normal medium, graded depolarizations did not accompany contractile responses. However, when the fiber was depolarized to a certain level, an increment of outward current appeared which partially inactivated with time. The threshold for delayed rectification in glycerol-treated fibers was almost the same as that of intact fibers in spite of the absence of contractile tension. The results suggest that the delayed rectification may be attributed at least in part to the surface membrane and that the contractile activation probably does not depend simply on the inactivating outward currents through the delayed rectification channel.

Sodium-dependent plateau potentials in cultured Retzius cells of the medicinal leech

1996 ◽  
Vol 76 (3) ◽  
pp. 1491-1502 ◽  
Author(s):  
J. D. Angstadt ◽  
J. J. Choo
Keyword(s):  
Outward Current ◽  
Channel Blockers ◽  
Plateau Potentials ◽  
Calcium Dependent ◽  
Current Pulses ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Prolonged Duration ◽  
Input Conductance ◽  
Retzius Cells

1. Individual leech Retzius (Rz) cells were removed from mid-body ganglia and plated in cell culture on concanavalin A or polylysine. Experiments on the majority of cells were performed after 6-11 days in culture. Isolated Rz cells were superfused with normal leech saline (NS), cobalt saline (Ca2+ replaced with Co2+), or one of a variety of other modified salines. 2. Prolonged plateau potentials (PPs) with durations ranging from several seconds to nearly 2 min were evoked in isolated Rz cells in response to 1-s depolarizing current pulses delivered under discontinuous current clamp. Some PPs terminated spontaneously while others were terminated with hyperpolarizing current pulses. PPs were associated with a dramatic increase in the input conductance of the neuron. The PP decayed slightly over time, and this decay was accompanied by a small decrease in the input conductance. 3. PP duration was enhanced by penetrating cells with electrodes containing tetraethylammonium (TEA) and by bathing cells in Co2+ saline, but PPs were evoked also in NS and using electrodes without TEA. The effects of TEA and Co2+ saline suggest that voltage-dependent and especially calcium-dependent outward currents normally suppress plateau formation. 4. PPs occurred most reliably in neurons with extensive neurite sprouting. Isolated somata with few or no neurites usually failed to express PP, although there were several exceptions to this trend. 5. PPs persisted when Ca2+ was replaced with either of the calcium channel blockers Co2+, Ni2+, or Mn2+, when 200 microM Cd2+ was added to normal saline, or when Na+ was replaced with Li+. In contrast, PPs were eliminated rapidly when Na+ was replaced with N-methyl-D-glucamine. 6. Isolated Rz cells also expressed repetitive PPs either spontaneously or in response to injection of sustained depolarizing current. Spontaneous repetitive PPs were suppressed by hyperpolarizing current. Repetitive PPs in isolated Rz cells are similar in many respects to the bursting electrical activity induced by Co2+ saline in Rz and other neurons in intact ganglia. 7. The ionic dependence and prolonged duration of PPs suggest that these responses are generated by a persistent voltage-dependent Na+ current. A quantitative computer simulation of PPs was achieved using a depolarization-activated Na+ conductance with very slow inactivation. Repetitive PPs were simulated by addition of a slow outward current in the form of an electrogenic pump.

scholarly journals Subtype-Specific Effects of Lithium on Glutamate Receptor Function

1999 ◽  
Vol 81 (4) ◽  
pp. 1506-1512 ◽  
Author(s):  
Nikolas B. Karkanias ◽  
Roger L. Papke
Keyword(s):  
Glutamate Receptor ◽  
Reversal Potential ◽  
Outward Current ◽  
Evoked Responses ◽  
Receptor Function ◽  
Specific Effects ◽  
Outward Currents ◽  
Low Concentrations ◽  
Agonist Concentration ◽  
High Concentrations

Subtype-specific effects of lithium on glutamate receptor function. We report that substitution of sodium with lithium (Li+) in the extracellular solution causes subtype-specific changes in the inward and outward currents of glutamate receptors (GluRs), without a shift in reversal potential. Li+produces an increase of inward and outward currents of α-amino-3-hydroxy-5-methyl-4-isoxazole propionate receptors and decreases in the currents of kainate (KA) and N-methyl-d-aspartate receptors. The greatest effect of Li+ was observed with GluR3. A concentration-response curve for GluR3 reveals that the potentiation caused by Li+ is greatest at saturating agonist concentrations. GluR1, which shows no potentiation by Li+at 100 μM KA, shows a small but significant potentiation at saturating KA and glutamate concentrations. The effects of Li+ on outward current, where Li+ is not the primary charge carrier, and the lack of reversal potential shift argue for a mechanism of potentiation not associated with Li+permeation. This potentiation of current is specific for Li+ because rubidium, although causing an increase of inward current, shifted the reversal potential and did not increase outward current. The effects of Li+ are different for KA, a weak desensitizing agonist, and glutamate, a strong desensitizing agonist, suggesting that Li+ might interact with a mechanism of desensitization. By using cyclothiazide (CTZ) to reduce desensitization of GluR3, we find that for low concentrations of KA and glutamate potentiation of the response by a combination of CTZ and Li+ is no greater than by CTZ or Li+ alone. However, at high concentrations of agonist, the potentiation of the response by a combination of CTZ and Li+ is significantly greater than by CTZ or Li+ alone. This potentiation was additive for glutamate but not for KA. At high agonist concentration in the presence of CTZ, the intrinsically lower desensitization produced with KA-evoked responses may preclude Li+ from potentiating the current to the same degree as it can potentiate glutamate-evoked responses. The additive effects of CTZ and Li+ were unique to the flop variant of GluR3.

scholarly journals Effects of Divalent Cations on Outward Potassium Currents in Leech Retzius Nerve Cells

2016 ◽  
Vol 17 (4) ◽  
pp. 309-314
Author(s):  
Zorica Jovanovic ◽  
Olgica Mihaljevic ◽  
Irena Kostic
Keyword(s):  
Action Potential ◽  
Neuronal Excitability ◽  
Divalent Cations ◽  
Extracellular Fluid ◽  
Outward Current ◽  
Potassium Currents ◽  
Nerve Cells ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Retzius Cells

Abstract The present study examines the effects of divalent metals, cadmium (Cd2+) and manganese (Mn2+), on the outward potassium currents of Retzius cells in the hirudinid leeches Haemopis sanguisuga using conventional two-microelectrode voltageclamp techniques. The outward potassium current is activated by depolarization and plays an important role in determining both the neuronal excitability and action potential duration. A strong inhibition of the fast current and a clear reduction in the late currents of the outward current with 1 mM Cd2+ were obtained, which indicated that both components are sensitive to this metal. Complete blockage of the fast and partial reduction of the slow outward currents was observed after adding 1 mM Mn2+ to the extracellular fluid. These data show that the outward K+ current in leech Retzius nerve cells comprises at least two components: a voltage-dependent K+ current and a Ca2+- activated K+ current. These observations also indicate that Cd2+ is more eff ective than Mn2+ in blocking ion fl ow through these channels and that suppressing Ca2+-activated K+ outward currents can prolong the action potential in nerve cells.

Detection of a Na+-H+ antiporter in cultured rat renal papillary collecting duct cells

1987 ◽  
Vol 253 (5) ◽  
pp. F889-F895 ◽  
Author(s):  
S. M. Wall ◽  
S. Muallem ◽  
J. A. Kraut
Keyword(s):  
Collecting Duct ◽  
Sodium Concentration ◽  
Significant Rise ◽  
Fluorescent Signal ◽  
Tetramethylammonium Chloride ◽  
Duct Cells ◽  
Papillary Collecting Duct ◽  
Collecting Duct Cells ◽  
High Concentrations ◽  
Extracellular Sodium

To examine whether Na+-dependent H+ transport is present in the papillary collecting duct, changes in intracellular pH (pHi) were evaluated in cultured papillary collecting duct cells acidified to a pHi of 6.3 and then placed into Na+-free or Na+-containing solutions. pHi was determined from changes in the fluorescent signal of the pH-sensitive dye BCECF. pHi did not change significantly when cells were placed in tetramethylammonium chloride- or KCl-containing solutions; however, a significant rise in pHi occurred when acid-loaded cells were placed in solutions containing 140 mM NaCl. The Na+-dependent rise in pHi was blocked by high concentrations of amiloride, but was not affected by alterations in membrane potential across the cell. The rate of rise in pHi was a function of extracellular sodium concentration with a Km for Na+ of 30 +/- 12 mM (n = 6). The properties of this Na+-dependent H+ efflux supports the presence of a Na+-H+ antiporter in the papillary collecting duct.

scholarly journals Contractility and 45Ca fluxes in heart muscle of flounder at a lowered extracellular NaCl concentration

1984 ◽  
Vol 109 (1) ◽  
pp. 201-207
Author(s):  
H. Gesser ◽  
A. Mangor-Jensen
Keyword(s):  
Sodium Chloride ◽  
Positive Inotropic Effect ◽  
Chloride Concentration ◽  
Sodium Concentration ◽  
Free Solution ◽  
Observable Effect ◽  
Resting Tension ◽  
Nacl Concentration ◽  
Extracellular Sodium ◽  
45Ca Efflux

The twitch force of isolated electrically paced ventricular strips of flounder, Platichthys flesus L., increased after lowering the extracellular sodium chloride concentration by 50 mmol l-1. This response was markedly reduced by replacing the sodium chloride with either Tris-HCl or sucrose, so that osmolarity was unchanged. The 45Ca efflux decreased and the 45Ca influx increased when the extracellular sodium concentration Nao+ was lowered. In contrast, changing only the osmolarity had no observable effect on these fluxes. An increased resting tension appeared in strips exposed to a Na+-, Ca2+-free solution. This was transient at an unchanged osmolarity but became permanent at an osmolarity lowered by 100 mosmol l-1. These results suggest that both a lowered Nao and a lowered osmolarity have a positive inotropic effect, due respectively to an increased cellular uptake of Ca2+ and a redistribution of cellular Ca2+.

scholarly journals Voltage Dependence of Slow Inactivation in Shaker Potassium Channels Results from Changes in Relative K+ and Na+ Permeabilities

2000 ◽  
Vol 115 (2) ◽  
pp. 107-122 ◽  
Author(s):  
John G. Starkus ◽  
Stefan H. Heinemann ◽  
Martin D. Rayner
Keyword(s):  
Potassium Channels ◽  
Outward Current ◽  
Negative Slope ◽  
Voltage Sensitivity ◽  
Slow Inactivation ◽  
Shaker Channels ◽  
Outward Currents ◽  
Voltage Dependent ◽  
Na Ions ◽  
Shaker Potassium Channels

Time constants of slow inactivation were investigated in NH2-terminal deleted Shaker potassium channels using macro-patch recordings from Xenopus oocytes. Slow inactivation is voltage insensitive in physiological solutions or in simple experimental solutions such as K+o//K+i or Na+o//K+i. However, when [Na+]i is increased while [K+]i is reduced, voltage sensitivity appears in the slow inactivation rates at positive potentials. In such solutions, the I-V curves show a region of negative slope conductance between ∼0 and +60 mV, with strongly increased outward current at more positive voltages, yielding an N-shaped curvature. These changes in peak outward currents are associated with marked changes in the dominant slow inactivation time constant from ∼1.5 s at potentials less than approximately +60 mV to ∼30 ms at more than +150 mV. Since slow inactivation in Shaker channels is extremely sensitive to the concentrations and species of permeant ions, more rapid entry into slow inactivated state(s) might indicate decreased K+ permeation and increased Na+ permeation at positive potentials. However, the N-shaped I-V curve becomes fully developed before the onset of significant slow inactivation, indicating that this N-shaped I-V does not arise from permeability changes associated with entry into slow inactivated states. Thus, changes in the relative contributions of K+ and Na+ ions to outward currents could arise either: (a) from depletions of [K+]i sufficient to permit increased Na+ permeation, or (b) from voltage-dependent changes in K+ and Na+ permeabilities. Our results rule out the first of these mechanisms. Furthermore, effects of changing [K+]i and [K+]o on ramp I-V waveforms suggest that applied potential directly affects relative permeation by K+ and Na+ ions. Therefore, we conclude that the voltage sensitivity of slow inactivation rates arises indirectly as a result of voltage-dependent changes in the ion occupancy of these channels, and demonstrate that simple barrier models can predict such voltage-dependent changes in relative permeabilities.

scholarly journals Sodium self-inhibition of human epithelial sodium channel: selectivity and affinity of the extracellular sodium sensing site

2007 ◽  
Vol 293 (4) ◽  
pp. F1137-F1146 ◽  
Author(s):  
Vincent Bize ◽  
Jean-Daniel Horisberger
Keyword(s):  
Steady State ◽  
Outward Current ◽  
Distal Colon ◽  
Ionic Selectivity ◽  
Outward Currents ◽  
Channel Selectivity ◽  
Fast Solution ◽  
Tight Epithelia ◽  
Protease Treatment ◽  
Extracellular Sodium

The epithelial Na+ channel (ENaC) is present in the apical membrane of “tight” epithelia in the distal nephron, distal colon, and airways. Its activity controls the rate of transepithelial sodium transport. Among other regulatory factors, ENaC activity is controlled by the concentration of extracellular Na+, a phenomenon named self-inhibition. The molecular mechanism by which extracellular Na+ concentration is detected is not known. To investigate the properties of the extracellular Na+ sensing site, we studied the effects of extracellular cations on steady-state amiloride-sensitive outward currents in Na+-loaded oocytes expressing human ENaC and compared them with self-inhibition of inward current after fast solution changes. About half of the inhibition of outward Na+ currents was due to self-inhibition itself and the rest might be attributed to conduction site saturation. Self-inhibition by extracellular Li+ was similar to that of Na+ except for slightly slower kinetics. Ionic selectivity of the inhibition for steady-state outward current was Na+ ≥ Li+ > K+. We estimated an apparent inhibitory constant ( KI) of ∼40 mM for extracellular Na+ and Li+ and found no evidence for a voltage dependence of the KI. Protease treatment induced the expected increase of the amiloride-sensitive current measured in high-Na+ concentrations which was due, at least in part, to abolition of self-inhibition. These results demonstrate that both self-inhibition and saturation play a significant role in the inhibition of ENaC by extracellular Na+ and that Na+ and Li+ interact in a similar way with the extracellular cation sensing site.

ABOLITION OF MAGNESIUM-INDUCED HYPOCALCAEMIA BY ACUTE THYRO-PARATHYROIDECTOMY IN THE CAT

1970 ◽  
Vol 64 (1) ◽  
pp. 150-158 ◽  
Author(s):  
S. Pors Nielsen
Keyword(s):  
Sodium Chloride ◽  
Flow Rate ◽  
Magnesium Chloride ◽  
Calcium Concentration ◽  
Plasma Calcium ◽  
Magnesium Concentration ◽  
Isotonic Sodium Chloride ◽  
Plasma Calcium Concentration ◽  
High Concentrations ◽  
Plasma Magnesium

ABSTRACT Intravenous infusion of isotonic magnesium chloride into young cats with a resultant mean plasma magnesium concentration of 7.7 meq./100 g protein was followed by a significant lowering of the plasma calcium concentration in 90 minutes. The rate of decrease of plasma calcium is consistent with the hypothesis that calcitonin is released by magnesium in high concentrations. There was no decrease in the plasma calcium concentration in cats of the same weight thyroparathyroidectomized 60 min before an identical magnesium chloride infusion or an infusion of isotonic sodium chloride at the same flow rate. The hypercalciuric effect of magnesium could not account for the hypocalcaemic effect of magnesium. Plasma magnesium concentration during magnesium infusion into cats with an intact thyroid-parathyroid gland complex was slightly, but not significantly higher than in acutely thyroparathyroidectomized cats.

scholarly journals Outcome of the use of 0.9% saline versus 0.45% saline for fluid rehydration in moderate and severe diabetic ketoacidosis in children

2021 ◽  
Vol 69 (1) ◽  
Author(s):  
Nora El Said Badawi ◽  
Mona Hafez ◽  
Heba Sharaf Eldin ◽  
Hend Mehawed Abdelatif ◽  
Shimaa Atef ◽  
...  
Keyword(s):  
Blood Glucose ◽  
Diabetic Ketoacidosis ◽  
Normal Saline ◽  
Sodium Concentration ◽  
Saline Group ◽  
Serum Electrolytes ◽  
Serum Chloride ◽  
Significant Difference ◽  
Rehydration Solution ◽  
The Moment

Abstract Background The debate for the optimum sodium concentration in the rehydration solution in diabetic ketoacidosis (DKA) persists till the moment. The aim was to compare the outcome of 0.9% saline versus 0.45% saline in children with moderate and severe (DKA) regarding the effect on serum electrolytes, duration of DKA resolution and the incidence of hyperchloremia. Results A retrospective analysis of 121 children with moderate or severe DKA was done. After the initial 4 h in which both groups received normal saline, patients were divided into two groups continuing on 0.9% (N=72) or switched to 0.45% saline (N=49). Serum chloride and Cl/Na ratios were significantly higher in 0.9% saline group at 4 and 8 h. The 0.9% saline group had significantly higher proportion of hyperchloremia at 4 and 8 h (P value: 0.002, 0.02). The median duration of correction of DKA (14 h among 0.9% saline versus 10 h among 0.45% saline) without significant difference (P value= 0.43). The change in plasma glucose, effective osmolarity, corrected Na levels were comparable between groups. Conclusion There is an unavoidable iatrogenically induced rise in serum chloride with higher incidence of hyperchloremia with the use of normal saline in rehydration of children presenting in DKA and shock. The use of 0.45% saline as post-bolus rehydration fluid is not associated with a decline in the corrected serum sodium concentration and does not affect the rate of correction of acidosis or rate of drop in blood glucose or duration of DKA resolution when compared to normal saline.

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