Changes in extracellular potassium and calcium in rat cerebellar cortex related to local inhibition of the sodium pump

1982 ◽  
Vol 395 (2) ◽  
pp. 108-114 ◽  
Author(s):  
A. Ullrich ◽  
R. Steinberg ◽  
P. Baierl ◽  
G. ten Bruggencate
Keyword(s):  
Cerebellar Cortex ◽  
Sodium Pump ◽  
Extracellular Potassium ◽  
Local Inhibition

Electric current generated by squid giant axon sodium pump: external K and internal ADP effects

1978 ◽  
Vol 235 (1) ◽  
pp. C63-C68 ◽  
Author(s):  
R. F. Abercrombie ◽  
P. de Weer
Keyword(s):  
Sodium Pump ◽  
Giant Axon ◽  
Pump Current ◽  
Membrane Resistance ◽  
Extracellular Potassium ◽  
Sodium Efflux ◽  
Steroid Sensitive ◽  
External Potassium ◽  
Loligo Pealei ◽  
External K

The operation of the sodium pump of giant axons of the squid, Loligo pealei, has been studied simultaneously in two independent ways: 1) by measuring sodium efflux with 22Na, and 2) by calculating the transmembrane current generated by the pump from measurements of membrane resistance and digitalis-sensitive membrane potential. In normal, untreated axons, the effect of increasing the external potassium concentration on both sodium efflux and pump current is similar, which suggests that Na:K pump stoichiometry remains relatively constant in the range of 0-20 mM external K. The data are compatible with a 3:2 Na:K ratio. In axons whose intracellular ADP level has been elevated by injection of L-arginine, a large, electrically silent, cardiotonic steroid-sensitive sodium efflux takes place in the absence of external potassium; this suggests that pump-mediated Na:Na exchange is 1:1 or electroneutral. Finally, elevation of external potassium levels causes the appearance, in high-ADP axons, of electrogenic pumping, with little effect on sodium efflux; hence, in contrast to what is seen in normal (low-ADP) axons, the charge translocated, per sodium ion extruded, increases sharply with increasing extracellular potassium levels.

Cardiotonic Steroids: Potential Endogenous Sodium Pump Ligands with Diverse Function11

2002 ◽  
Vol 227 (8) ◽  
pp. 561-569 ◽  
Author(s):  
Renata I. Dmitrieva ◽  
Peter A. Doris
Keyword(s):  
Binding Site ◽  
Intracellular Signaling ◽  
Sodium Pump ◽  
Cellular Level ◽  
Extracellular Potassium ◽  
Sodium Potassium ◽  
A Cell ◽  
Body Fluid Balance ◽  
Sodium And Potassium ◽  
Insight Into

The highly conserved cardiotonic steroid (CS) binding site present on the ubiquitous membrane sodium pump, sodium, potassium-ATPase, appears to have been conserved by no force other than its capacity to bind CS: a family that includes plant-derived cardiac glycosides and putative endogenous vertebrate counterparts. Binding of ligand is inhibited by increased extracellular potassium. This implies functional coordination because inhibition of the sodium pump would be counterproductive when extracellular potassium is elevated. The interesting biology of the CS binding site continues to stimulate investigations into the identity of endogenous ligands, their role as pump regulators at the cellular level, and as mediators of body fluid balance and blood pressure regulation. In addition to inhibition of sodium and potassium transport, there is considerable recent evidence suggesting that the sodium pump may act as a cell signaling receptor activated by CS binding and responding by coordination of intracellular signaling pathways that can be dependent on and also independent of the reduction in transmembrane ion flux resulting directly from pump inhibition. This signaling may influence cell survival, growth, and differentiation. Recent insight into the biology of pump regulation by CS is reviewed.

Alkaline and acid transients in cerebellar microenvironment

1983 ◽  
Vol 49 (3) ◽  
pp. 831-850 ◽  
Author(s):  
R. P. Kraig ◽  
C. R. Ferreira-Filho ◽  
C. Nicholson
Keyword(s):  
Neuronal Activity ◽  
Cerebellar Cortex ◽  
Stimulus Frequency ◽  
Ringer Solution ◽  
Weak Acid ◽  
Ion Concentration ◽  
Extracellular Potassium ◽  
Base Line ◽  
Extracellular Potassium Concentration ◽  
The Brain

1. Extracellular pH (pHo) was measured in the cerebellar cortex of the rat using a recently developed liquid membrane ion-selective micropipette (ISM). pHo was determined during stimulus-evoked neuronal activity, elevated extracellular potassium concentration, [K+]o, spreading depression (SD), and complete ischemia. In many experiments [K+]o was simultaneously determined. 2. A train of local surface stimuli (LOC) produced an initial alkaline shift in pHo from a base line of 7.20-7.30 to 7.25-7.35. This was followed by a long-lasting acid phase that reached a plateau of 7.05-7.15 after 64 s of stimulation. pHo decrease was related to stimulus frequency, intensity, and duration. 3. Superfusion with Ringer solution containing manganese ions rapidly abolished parallel fiber-induced Purkinje cell synaptic depolarization together with the alkaline shifts while enhancing the acid shifts. 4. Superfusion of the cerebellar cortex with Ringer solution containing increasingly elevated [K+] progressively lowered pHo to a plateau of 6.95-7.05. The acidification occurred in the presence of ouabain but was reversed on return to the normal [K+]o or with the addition of the glycolytic blocker, fluoride. Stimulus-evoked alkaline shifts were enhanced by K+-Ringer superfusion. These experiments suggested that the acid shift was due to the metabolic production of an anion, possibly lactate. 5. Elevation of [K+]o above 8-12 mM often produced oscillation in pHo and [K+]o with a period of about 40 s. Sometimes these oscillations ended in a spontaneous SD or SD could be evoked by stimulation. Under these conditions of raised [K+]o, the SD consisted of a very pronounced alkaline transient followed by a small, long-lasting acid shift. When SD was induced by conditioning the cerebellum with proprionate or lowered NaCl, the alkaline phase was reduced and the acid enhanced. 6. Complete ischemia began with a progressive decrease of pHo and rise in [K+]o. When [K+]o reached 12 mM, a second more rapid rise in [K+]o to 40 mM or more occurred. This was correlated with 0.1-0.2 pHo transient increase similar to that seen during SD. pHo eventually reached a plateau of 6.60-6.80, close to neutrality. 7. Superfusion with Ringer solution containing acetazolamide immediately altered pHo homeostasis by increasing base-line pHo by about 0.10 and enhanced the induced pHo changes. These results suggest that carbonic anhydrase (CA) is important for acute buffering of the brain extracellular microenvironment. 8. The above results were interpreted in terms of changes in extracellular strong ion concentration differences ( [SID]o), extracellular concentration of total weak acid ( [Atot]o) and partial pressure of CO2 (Pco2) in the brain microenvironment. The results indicate that neuronal activity produces changes in many of the constituents of the microenvironment.

High extracellular potassium, and not extracellular glutamate, is required for the propagation of spreading depression

1995 ◽  
Vol 73 (5) ◽  
pp. 2107-2114 ◽  
Author(s):  
T. P. Obrenovitch ◽  
E. Zilkha
Keyword(s):  
Spreading Depression ◽  
Glutamate Uptake ◽  
Extracellular Fluid ◽  
Extracellular Potassium ◽  
Fluid Composition ◽  
Extracellular Glutamate ◽  
Microdialysis Probe ◽  
Local Inhibition ◽  
Artificial Cerebrospinal Fluid ◽  
Positive Effect

1. Cortical spreading depression (SD) is a propagating transient suppression of electrical activity associated with depolarization, which may contribute to the pathophysiology of important neurological disorders, including cerebral ischemia and migraine. The purpose of this study is to ascertain whether SD propagation depends on local accumulation of extracellular K+ or glutamate. 2. Propagating SD recorded through microdialysis probes perfused with artificial cerebrospinal fluid (ACSF) was much smaller than that recorded with conventional glass microelectrodes, presumably because some SD-induced transient changes in the extracellular fluid composition were buffered by ACSF. We have exploited this effect to determine whether perfusion with a medium containing increasing amounts of K+ and/or glutamate favors SD propagation. 3. Increasing the concentration of K+ (15-60 mmol/l) in the perfusion medium dose-dependently restored SD propagation, whereas application of 100-250 mumol/l glutamate through the microdialysis probe had no effect. Superimposing 200 mumol/l glutamate onto 15 and 30 mmol/l K+ did not further improve the restoration of SD propagation by K+. 4. Because potent uptake mechanisms may efficiently clear exogenous glutamate from the extracellular space, the effect of local inhibition of high-affinity glutamate uptake was also studied. Perfusion of the recording microdialysis probe with 1 mmol/l L-trans-pyrrolidine-2,4-dicarboxylate (L-trans-PDC), either alone or together with 200 mumol/l glutamate, had no effect. In addition, L-trans-PDC did not potentiate the positive effect of 30 mmol/l K+ on SD propagation. 5. These results strongly suggest that high extracellular K+, and not extracellular glutamate, is the driving force sustaining SD propagation.(ABSTRACT TRUNCATED AT 250 WORDS)

scholarly journals Effects of extracellular calcium and potassium on the sodium pump of rat adrenal glomerulosa cells

2001 ◽  
Vol 280 (1) ◽  
pp. C119-C125 ◽  
Author(s):  
Douglas R. Yingst ◽  
Joanne Davis ◽  
Rick Schiebinger
Keyword(s):  
Sodium Pump ◽  
Calcium Influx ◽  
Calcium Ionophore ◽  
Extracellular Calcium ◽  
Intracellular Free Calcium ◽  
Free Calcium ◽  
Extracellular Potassium ◽  
A 23187 ◽  
Pump Activity ◽  
Glomerulosa Cells

Because the activity of the sodium pump (Na-K-ATPase) influences the secretion of aldosterone, we determined how extracellular potassium (Ko) and calcium affect sodium pump activity in rat adrenal glomerulosa cells. Sodium pump activity was measured as ouabain-sensitive 86Rb uptake in freshly dispersed cells containing 20 mM sodium as measured with sodium-binding benzofluran isophthalate. Increasing Ko from 4 to 10 mM in the presence of 1.8 mM extracellular calcium (Cao) stimulated sodium pump activity up to 165% and increased intracellular free calcium as measured with fura 2. Increasing Ko from 4 to 10 mM in the absence of Cao stimulated the sodium pump ∼30% and did not increase intracellular free calcium concentration ([Ca2+]i). In some experiments, addition of 1.8 mM Cao in the presence of 4 mM Ko increased [Ca2+]i above the levels observed in the absence of Cao and stimulated the sodium pump up to 100%. Ca-dependent stimulation of the sodium pump by Ko and Cao was inhibited by isradipine (10 μM), a blocker of L- and T-type calcium channels, by compound 48/80 (40 μg/ml) and calmidizolium (10 μM), which inhibits calmodulin (CaM), and by KN-62 (10 μM), which blocks some forms of Ca/CaM kinase II (CaMKII). Staurosporine (1 μM), which effectively blocks most forms of protein kinase C, had no effect. In the presence of A-23187, a calcium ionophore, the addition of 0.1 mM Cao increased [Ca2+]i to the level observed in the presence of 10 mM Ko and 1.8 mM Cao and stimulated the sodium pump 100%. Ca-dependent stimulation by A-23187 and 0.1 mM Cao was not reduced by isradipine but was blocked by KN-62. Thus, under the conditions that Ko stimulates aldosterone secretion, it stimulates the sodium pump by two mechanisms: direct binding to the pump and by increasing calcium influx, which is dependent on Cao. The resulting increase in [Ca2+]i may stimulate the sodium pump by activating CaM and/or CaMKII.

Extracellular potassium in rat cerebellar cortex during acute and chronic lithium application

1980 ◽  
Vol 192 (1) ◽  
pp. 287-290 ◽  
Author(s):  
Axel Ullrich ◽  
Peter Baierl ◽  
Gerrit ten Bruggencate
Keyword(s):  
Cerebellar Cortex ◽  
Extracellular Potassium

Severe Drooling and Treatment With Botulinum Toxin

2012 ◽  
Vol 21 (1) ◽  
pp. 15-21
Author(s):  
Merete Bakke ◽  
Allan Bardow ◽  
Eigild Møller
Keyword(s):  
Botulinum Toxin ◽  
Side Effects ◽  
Health Risk ◽  
Flow Rate ◽  
Clinical Evidence ◽  
Acetylcholine Release ◽  
Psychosocial Problems ◽  
Rate Reduction ◽  
Local Inhibition ◽  
Surgical Treatments

Severe drooling is associated with discomfort and psychosocial problems and may constitute a health risk. A variety of different surgical and non-surgical treatments have been used to diminish drooling, some of them with little or uncertain effect and others more effective but irreversible or with side effects. Based on clinical evidence, injection with botulinum toxin (BTX) into the parotid and submandibular glands is a useful treatment option, because it is local, reversible, and with few side effects, although it has to be repeated. The mechanism of BTX is a local inhibition of acetylcholine release, which diminishes receptor-coupled secretion and results in a flow rate reduction of 25–50% for 2–7 months.

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