Adrenaline and the electrogenic sodium pump in Rana catesbeiana sympathetic ganglion cells.

The effect of adrenaline on the Na+-pump in bullfrog (Rana catesbeiana) sympathetic ganglion cells was studied by use of electrophysiological methods. The rate of removal of excess Na+ injected into a ganglion cell was increased by adrenaline. The K+-activated hyperpolarization of cell membrane, which might be produced by an electrogenic Na+-pump, was also increased by adrenaline. These results suggested that adrenaline was able to accelerate the Na+-pump, possibly the electrogenic Na+-pump.     

The effect of adrenaline on the electrogenic Na+ pump in cardiac muscle cells

Electrogenic Na+ pump currents during K+-activated hyperpolarizations of bullfrog atrium muscle fibres are increased by adrenaline. The log dose-response relation between these currents and activating K+ concentrations is expressed by a sigmoidal curve, which is shifted in parallel to the left by adrenaline. It is suggested that adrenaline increases the rate of Na+ extrusion without increasing the Na/K coupling ratio and total number of pumping sites.     

Evidence of abnormalities in net sodium and potassium fluxes in erythrocytes of patients with essential hypertension]

A new and simple laboratory test for measuring net Na+ and K+ fluxes in Na+-loaded/K+-depleted human erythrocytes was developed and applied to hypertension. Moderate essential hypertension was characterized by a constant increase in net K+ influx; more severe cases showed a drop in net Na+ efflux. Na+ and K+ erythrocyte fluxes were found to be normal in hypertension of renal origin.     

Evidence for a Na+/NH4+ exchange in the gill of trout adapted to sea water: adrenergic control]

A Na+/NH4+ exchange similar to that characterizing the fish gill in fresh water was shown to function in the trout adapted to sea water with the help of the head perfusion technique. This exchange stimulated by adrenaline through beta adrenoreceptors and inhibited by amiloride added to the external medium.     

Cl<Superscript>–</Superscript> affects the function of the GABA cotransporter rGAT1 but preserves the mutal relationship between transient and transport currents

The effects of reducing external Cl- on the electrophysiological properties of the Na+/Cl(-)-dependent GABA transporter rGAT1 expressed in Xenopus oocytes were investigated. In agreement with a recently proposed kinetic scheme, the effects of Cl- are complex but preserve the mutual relationship that links the transport-associated current, I(tr), measured in saturating GABA concentration, and the transient current, I(pre), recorded in the absence of GABA following a voltage step from the holding potential Vh to V. In particular, I(tr) (V) - I(tr) (Vh) = r integral I(pre) (V) dt, where r is the relaxation rate of I(pre) at the same membrane potential and Cl- concentration. The model also predicts a relationship between charge relaxation rate and apparent affinity for GABA, which is also verified in the presence of lowered Na+ or Cl- concentrations. In these conditions, the binding rate of GABA to the transporter is increased. All these effects are consistent with the hypothesis that interaction of the organic substrate with rGAT1 induces a conversion from a capacitive to a conductive mode of operation without strongly altering either the amount or the rate of charge movement.     

Concerning the ionic basis of presynaptic inhibition.

The superfused rat cuneate nucleus has been used to investigate the sensitivity of primary afferent terminals and of evoked primary afferent depolarization (PAD) to alterations in extracellular K+ and Cl- ions levels. Results indicate that PAD is caused by an efflux of Cl- from primary afferent terminals rather than by an increase in extracellular K+.     

Contribution of the Na+/K+-pump to the membrane potential

The inward movement of sodium ions and the outward movement of potassium ions are passive and the reverse movements against the electrochemical gradients require the activity of a metabolism-driven Na+/K+-pump. The activity of the Na+/K+-pump influences the membrane potential directly and indirectly. Thus, the maintenance of a normal electrical function requires that the Na+/K+-pump maintain normal ionic concentrations within the cell. The activity of the Na+/K+-pump also influences the membrane potential directly by generating an outward sodium current that is larger when the Na+/K+-pump activity is greater. The activity of the Na+/K+-pump is regulated by several factors including the intracellular sodium concentration and the neuromediators norepinephrine and acetylcholine. The inhibition of the Na+/K+-pump can lead indirectly to the development of inward currents that may cause repetitive activity. Therefore, the Na+/K+-pump modifies the membrane potential in different ways both under normal and abnormal conditions and influences in an essential way many cardiac functions, including automaticity, conduction and contraction. Key words. Active transport of ions; cardiac tissues; electroneutral and electrogenic Na+/K/-pump; control of Na+/K+-pump; normal and abnormal electrical events.     

Characterization of the (Na+-K+)-ATPase from endometrial plasma membranes of immature mammals]

The (Na+-K+)-ATPase in plasma membrane from Mammiferous endometrium is characterized by the Mg/ATP ratio equal to one, and by a distinct affinity for Na+ (1.3 mM) and K+ (2 mM). The activity is maximum for pH 7.4-7.5 in presence of Mg++ 2mM and ATP 2 mM, Na+ 140 mM and K+ 10 mM.     

Purification from human plasma of endogenous sodium transport inhibitor(s)

Na+,K+-ATPase inhibitors extracted from plasma of healthy human subjects displaced 3H-ouabain binding to human erythrocytes and inhibited the Na+ efflux catalyzed by the Na+,K+-pump and unexpectedly the Na+,K+-cotransport system without alteration of the Na+,Na+-exchange or the Na+ passive permeability. This suggests the presence in healthy human plasma of endogenous factors with ouabain-like and furosemide-like activities.     

Ouabain action on sodium,chloride and fluid transport in rabbit jejunum and ileum

Riassunto É stato studiato l'effetto della ouabaina sul trasporto di Na, Cl e fluido in digiuno e ileo isolato di coniglio. Mentre in entrambi i tratti intestinali il flusso mucosa-serosa di Na è inibito dal glicoside, il flusso nello stesso senso di Cl, di cui è stata dimostrata una componente attiva, non viene modificato. Poichè inoltre il trasporto di fluido viene inibito dalla ouabaina in misura diversa in digiuno e in ileo, si suggerisce la presenza di sistemi ATPasici non ouabaino-sensibili accanto alla Na–K ATPasi sensibile alla ouabaina che si ammette essere responsabile del trasporto di Na.

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Experiments not reported in this paper show that ouabain 5×10^–4 M does not enhance the ileal Na influx inhibition and also does not modify the Cl influx. Moreover ouabain 10^–4 M affects jejunal Na influx to a less significant extent than 5×10^–4 M.     

Lithium exchange in from epithelium: determination of unidirectional flux using the stable isotopes 6Li and 7Li in an ionic analyzer]

The use of the stable isotopes 6 and 7 of lithium, and detection with the ionic analyser, allow the measurement of unidirectional transepithelial Li-fluxes, between "external" and "internal" solutions which both contain 80% Na and 20% Li. Efflux was found to be bigger than influx. An important lag-phase on the curve, reveals the interference of a Li-compartment, with a high capacity, in the epithelium itself.     

The (Na+ + K+)-ATPase activity in brain of Quaking mice.

The (Na+ 4 K+)- and Mg2+-dependent ATPase distribution in several brain areas has been investigated in Quaking mutant mice characterized by myelin deficiency. A marked decrease of (Na+ + K+)-ATPase activity has been found in limbic structures, hypothalamus and cerebellum. The Mg2+-dependent activity did not change. A possible involvement of the impairment of the (Na+ + K+)-ATPase activity in the seizure susceptibility of this mice is discussed.     

The action of ouabain in promoting the release of catecholamines.

It is suggested that ouabain promotes catecholamine release by causing a rise in intracellular Na+ which, in turn, causes an elevated steady-state level of intracellular Ca2+. It is suggested that the Na+-K+-ATPase is not directly involved in exocytosis at either adrenergic or cholinergic synapses.     

Inhibition of hepatic Na +, K + -adenosinetriphosphatase in taurolithocholate-induced cholestasis in the rat.

Na +, K + -adenosinetriphosphatase (Na +, K + -ATPase) activity was decreased in liver plasma membranes from rats in which cholestasis had been induced by i.v. administration of sodium taurolithocholate (5 mumoles/100 g b. wt). Incubation of liver plasma membranes with taurolithocholate (10--1300 muM) caused significant and dose dependent reductions of Na +, K + -ATPase activity at taurolithocholate concentrations above 100 muM. These findings lend support to the hypothesis that cholestasis induced by monohydroxy bile acids is at least partially the result of an inhibition of hepatic Na +, K + -ATPase activity.     

Effect of ouabain on volume regulation of rabbit kidney cortex slices in hypo-osmotic media

The volume regulation process at work in rabbit kidney cortex slices submitted to hypo-osmotic media show both a swelling limitation and a volume readjustment phase. Swelling limitation is Na+ dependent and is blocked by ouabain 10(-3) M. There is, however, no need to implicate the activity of a ouabain sensitive Na+ /K+ pump in this process.     

Cardiac cellular electrophysiology: past and present

The time-course of the cardiac action potential can be accounted for in terms of ionic currents crossing the cell membranes. Depolarizing current is carried by Na+ or Ca2+ entering the cells, repolarizing current by K+ leaving the cells. Membrane permeability for the passive movement of these ions is thought to be voltage-dependent as well as time-dependent. Net transfer of charge may also result from active transport, 2 Na+ out against 1 K+ in; or coupled exchange, 3 or 4 Na+ in against 1 Ca2+ out. This review follows the path by which present-day knowledge has been reached. It also gives a few examples to illustrate that electrophysiology has provided concepts useful to clinical cardiology.     

Sodium channels in cardiac Purkinje cells

Sodium (Na+) currents are responsible for excitation and conduction in most cardiac cells, but their study has been hampered by the lack of a satisfactory method for voltage clamp. We report a new method for low resistance access to single freshly isolated canine cardiac Purkinje cells that permits good control of voltage and intracellular ionic solutions. The series resistance was usually less than 3 omega cm2, similar to that of the squid giant axon. Cardiac Na+ currents resemble those of nerve. However, Na+ current decay is multiexponential. The basis for this was further studied with cell-attached patch clamp recording of single Na+ channel properties. A prominent characteristic of the single channels was their ability to reopen after closure. There was also a long opening state that may be the basis for a small very slowly decaying Na+ current. This rare long opening state may contribute to the Na+ current during the action potential plateau.     

The role of distinct membrane components of the enzyme in the ouabain sensitivity of Na+/K+ ATPase]

Purified plasma membranes from a cell line derived from the murine plasmocytoma MOPC 173 exhibited a 50% inhibition of the Na+K+ ATPase by 120 muM ouabain. EDTA treatment of such membranes induced a drop in the ouabain concentration needed for 50% inhibition to 0.4 muM. Supernatants obtained after EDTA treatment were able to complement with Ca(++) + Mg++ the washed EDTA treated membranes which recover their original resistance.     

A histochemical demonstration of the Na+ + K+-ATPase activity in the thyroid and the effect of cyclic adenosine monophosphate (c-AMP).

With a suitable modification of the Farquhar and Palade technique the Na+ + K+-ATPase activity in guinea-pig thyroid is demonstrated. The addition of c-AMP (5 X 10(-6) M or 1.5 X 10(-5) M) to the incubation media produced an apparent intensification of the Na+ + K+ -ATPase activity in the thyroid.     

Decreased monosaccharide transport in renal brush-border membrane vesicles of spontaneously hypertensive rats

Na(+)-dependent D-glucose and D-galactose transport were studied in brush-border membrane vesicles (BBMVs) from kidney cortex isolated from both spontaneously hypertensive rats (SHR) and their normotensive genetic control Wistar-Kyoto (WKY) rats. Initial rates and accumulation ratios of Na(+)-dependent D-glucose and D-galactose transport were significantly lower in SHR compared with WKY, the observed decreases being similar for both substrates. To explain the reduction in sugar transport by renal BBMVs, the density of Na(+)-dependent sugar cotransporters was studied in BBMVs from kidney cortex isolated from SHR and WKY rats. Phlorizin-specific binding and Western blot analysis indicated a reduction in the density of the cotransporters in SHR relative to WKY rats. This reduction was similar to those found for the initial rates and accumulation ratios for D-glucose and D-galactose in SHR. Na+ uptake, studied using 22Na+, was significantly increased in SHR, so the observed reduction in sugar transport could be due to disruption of the Na+ gradient between renal BBMVs in SHR. Furthermore, a significant decrease in the activity of Na(+)-K(+)-ATPase was observed in SHR. In conclusion, changes in the density of the Na(+)-dependent sugar cotransporter and in the Na+ gradient across the brush-border membranes might be involved in the observed reduction in sugar transport by renal BBMVs from SHR.