Increase In Na Permeability Research Articles

Effect of arachidonic acid, fatty acids, prostaglandins, and leukotrienes on volume regulation in Ehrlich ascites tumor cells.

Arachidonic acid inhibits the cell shrinkage observed in Ehrlich ascites tumor cells during regulatory volume decrease (RVD) or after addition of the Ca ionophore A23187 plus Ca. In Na-containing media, arachidonic acid increases cellular Na uptake under isotonic as well as under hypotonic conditions. Arachidonic acid also inhibits KCl and water loss following swelling in Na-free, hypotonic media even when a high K conductance has been ensured by addition of gramicidin. In isotonic, Na-free medium arachidonic acid inhibits A23187 + Ca-induced cell shrinkage in the absence but not in the presence of gramicidin. It is proposed that inhibition of RVD in hypotonic media by arachidonic acid is caused by reduction in the volume-induced Cl and K permeabilities as well as by an increase in Na permeability and that reduction in A23187 + Ca-induced cell shrinkage is due to a reduction in K permeability and an increase in Na permeability. The A23187 + Ca-activated Cl permeability in unaffected by arachidonic acid. PGE2 inhibits RVD in Na-containing, hypotonic media but not in Na-free, hypotonic media, indicating a PGE2-induced Na uptake. PGE2 has no effect on the volume-activated K and Cl permeabilities. LTB4, LTC4 and LTE4 inhibit RVD insignificantly in hypotonically swollen cells. LTD4, moreover, induces cell shrinkage in steady-state cells and accelerates the RVD following hypotonic exposure. The effect of LTD4 even reflects a stimulating effect on K and Cl transport pathways. Thus none of the leukotrienes show the inhibitory effect found for arachidonic acid on the K and Cl permeabilities. The RVD response in hypotonic, Na-free media is, on the other hand, also inhibited by addition of the unsaturated oleic, linoleic, linolenic and palmitoleic acid, even in the presence of the cationophor gramicidin. The saturated arachidic and stearic acid had no effect on RVD. It is, therefore, suggested that a minor part of the inhibitory effect of arachidonic acid on RVD in Na-containing media is via an increased synthesis of prostaglandins and that the major part of the arachidonic acid effect on RVD in Na-free media, and most probably also in Na-containing media, is due to the inhibition of the volume-induced K and Cl transport pathways, caused by a nonspecific detergent effect of an unsaturated fatty acid.

Two subtypes of sodium channel with tetrodotoxin sensitivity and insensitivity detected in denervated mammalian skeletal muscle

The action potential (AP) in most nerve and muscle preparations depends upon an increase in Na permeability which is blocked by nanomolar concentrations of the neurotoxins saxitoxin (STX) and tetrodotoxin (TTX). In some excitable tissues lacking mature innervation, a toxin-resistant AP has been described by electrophysiological results. However, multiple attempts to detect corresponding toxin-resistant Na channels with radiolabelled STX and TTX have been unsuccessful. We report here the detection of Na channels with low-affinity binding of STX and TTX, accounting for 50–60% of the Na channels in rat hindlimb muscle 4–5 days after denervation.

Effects of the Na ionophore monensin on the contractile response and the movements of monovalent cations in the vascular smooth muscle of rabbit aorta.

The effects of monensin, a Na ionophore, on the muscle contraction and the movements of monovalent cations were investigated in rabbit aorta. Experiments were conducted in the presence of phentolamine (10(-6) M) to avoid the vasoactive effect of monensin due to the release of endogenous catecholamine. Both monensin (2 X 10(-5) M) and ouabain (2 X 10(-5) M), added separately, produced a small and slowly developing contraction, whereas simultaneous application of these agents produced more rapid and greater contraction. Verapamil (10(-6) M) decreased the contraction by 75%. Ouabain gradually increased cellular Na content. Monensin augmented the ouabain-induced Na increase. Further, the loss of cellular Na into Na deficient solution was enhanced by monensin. Low temperature (0.5 degrees C) inhibited the monensin-induced increase in Na permeability. The relaxation of noradrenaline-contraction induced by a K-readmission was inhibited by ouabain but not by monensin. These results suggest that monensin increases Na movement down its electrochemical gradient, augments cellular Na accumulation when the Na pump is inhibited by ouabain, and induces muscle contraction, and that the contraction induced by monensin and ouabain is mainly due to an increased Ca influx through voltage sensitive Ca channels.

The influence of calcium-free media on the electrical properties of the isolated toad lens

Anterior and posterior faces of toad lenses were isolated in a glass chamber and a glass electrode impaled into the fibers. The potential differences (p.d.) and electrical resistances of each surface and of the whole lens were measured before and after replacing the 1 m m-Ca-rich bathing solutions with a Ca-free 1 m m-EGTA Ringer. Ca-free anterior bathing solution reduced the p.d. only across the anterior face from 67 to 51 mV and the anterior face resistance from 331 to 304 Ω/cm 2. The changes were reversible within 35 min. Ca-free posterior bathing solution reduced the p.d. across the posterior face from 49 to 36 mV and posterior face resistance from 440 to 364 ohm. cm 2. These changes also were reversible. The effects on the translenticular p.d. were the algebraic addition of the effects on the individual surfaces: Ca-free Ringer's solution on the posterior side increases p.d. and short-circuit current by making the posterior barrier (in series with the epithelium) more permeable. Ca-free Ringer's solution on the anterior side reduces p.d. and short-circuit current by making the anterior side barrier more permeable and shunting out the Na pump located in the lens epithelium. In the absence of Na in the bathing solution, removal of Ca from the anterior solution reduced the anterior face p.d. by 14 mV and the electrical resistance from 407 to 351 ohm.cm 2. Removal of Ca from the posterior bathing solution (in the absence of Na) reduced the posterior face p.d. by 13 mV and the electrical resistance from 439 to 353 ohm.cm 2. It is concluded that the effects of free Ca across the anterior face is mainly due to an increase in Na permeability. The effects of free Ca across the posterior face is due to an increase in permeability not only to Na but to other ions in the solution.

Ion Selective Effects of Salicylate on Antral Mucosa

The effects of luminal salicylate, 5mM, were measured on rates of ion transport by isolated antral mucosa. At neutral luminal pH, salicylate increases Na and decreases Cl permeability. Salicylate does not alter net Na transport but decreases net Cl secretion. At luminal pH 4, the effects of salicylate can be arbitrarily divided into two phases. The intitial phase is associated with an increase in Na and marked decrease in Cl permeability. Subsequently, a greater increase in Na permeability and a marked increase in Cl permeability occurs. Active Na transport persists in the presence of salicylate at pH 4. Indirect evidence also suggests that Cl secretion persists under these conditions, buy at a reduced rate. The rate of luminal acid acid loss also increases in the presence of salicylate. A 4-fold increase in salicylate concentration or decrease in luminal pH from 4 to 3 did not appear to intensify the effects observed for 5 mM salicylate at pH 4. The increase in cation and decrease in anion permeability observed at pH 7 and initially at pH 4 are compatible with an influence of a negative charge of the salicylate anion. The subsequent changes observed in the presence of acid also are compatible with the concept that as the mucosa becomes overwhelmed with acid, a nonspecific increase in permeability occurs. However, the effect of salicylate on active Cl transport is largely independent of acid diffusing into the mucosa.

The effect of ions and drugs on the initiation and conduction of peristaltic wave in the heart of Ciona intestinalis

1. The effect of ions and drugs on the initiation and the conduction of peristaltic wave was studied on the heart of a tunicate, Ciona intestinalis. 2. The conduction of peristaltic wave was blocked by the replacement of [Na] o by choline, but not by the addition of Mn ions (20 mM) or the removal of [Ca] o. 3. Procaine (1 mM) inhibited the pacemaker activity, but did not block the conduction of peristaltic wave. The heart-beat was not influenced by tetrodotoxin (10 −6 g/ml) or picrotoxin (10 −3 g/ml). 4. These results indicate that the action potential in the muscle cells is mainly associated with the regenerative increase in Na-permeability.

Potassium rectifications of the starfish oocyte membrane and their changes during oocyte maturation.

1. The current-voltage relations of the oocyte membrane of the starfish, Asterina pectinifera, and their changes during maturation were investigated using current-clamp techniques. 2. The resting potential of the oocyte membrane in sea water was found to be determined by the diffusion potential of K ions. 3. In the absence of Na and Ca inward currents the steady-state current-voltage relation of the oocyte membrane had inward-going K rectification at membrane potentials more negative than -65 mV and outward-going K rectification at potentials more positive than -30 mV, forming a S-shaped I-V curve. 4. A negative resistance region of the steady-state I-V curve was revealed with voltage-clamp technique in the potential range between -65 and -30 mV. 5. Transient K activation occurred when the membrane was brought from a resting potential of about -75 mV to potentials more positive than -20 mV, and this was immediately followed by K inactivation. Accordingly, the steady-state I-V relation showed only slight outward-going rectification. 6. At the beginning of meiosis, which is signalled by break-down of the nucleus, the limiting slope conductance in the inward rectifying region of the I-V curve decreased sevenfold. The cell membrane lost its selective permeability to K ions and was depolarized from -70 to between -20 and OmV in standard artificial sea-water. The depolarized resting potential was partly due to the relative increase in Na permeability. K conductance began to increase again within 30 min after breakdown of the nucleus. The resting potential became gradually larger and eventually attained -70 mV in the mature egg. 7. In the mature egg, K activation upon depolarization was no longer followed by inactivation. Accordingly, the slope conductance in the outward rectifying region of the I-V curve increased. 8. The action potential was augmented at the stage of nuclear breakdown. Thereafter the maximum rate of rise decreased and the duration of the action potential shortened. These changes were caused primarily by changes in K conductance during maturation. 9. Fertilization of the egg during the maturation process did not affect the changes in the I-V relation described above, except for a transient change of the membrane permeability upon fertilization.

The electrogenic sodium pump in the hyperpolarizing and secretory effects of pancreozymin in the pancreatic acinar cell.

1. Transmembrane potential, effective membrane resistance, and amylase release were recorded simultaneously from acinar cells of isolated rat pancreas perfused with Krebs-Henseleit solution. 2. The hyperpolarizing effect of pancreozymin (Pz) was confirmed by perfusing with a solution containing 5 m-u. Pz/ml. 3. The hyperpolarizing effect of Pz disappeared in the following environments: (a) in low ambient temperature, (b) in K-free medium, (c) in low Na medium, and (d) in the presence of ouabain. In these environments, transient depolarization was frequently observed immediately after stimulation. It is suggested that there are two components in the effect of Pz on the membrane potential of the acinar cells: transient depolarization which coincides with an increase in Na permeability in the initial phase, and continuous hyperpolarization due to an electrogenic Na pump which conceals transient depolarizing phase when the pump is dominant. 4. The secretory effect of Pz was inhibited under conditions that suppressed the electrogenic Na pump. It is proposed that the Na pump activated by Pz maintains the passive Na-influx, increases [Ca2+]i, and, in consequence, uphold the amylase output during continuous stimulation. 5. A medium which was used to bathe the sectioned pancreas with Pz was found to contain a substance which depolarized the acinar cells.

The ionic permeability of the amphibian oocyte in the presence or absence of external calcium.

AbstractThe membrane potential of the Rana oocyte, as determined by intracellular microelectrodes, ranges from approximately −40 to −70 mV (inside negative). Upon removal of external Ca, a large, rapid depolarization in membrane potential occurs. The depolarization is reversible by both Ca and Mg. In the presence of Ca, the magnitude of the membrane potential is primarily dependent on the K distribution across the oocyte membrane with a lesser but significant Na dependence. Upon Ca removal, the Na dependence is greatly increased, indicating an increased Na permeability. Direct measurements of Na, K and Cl permeability by tracer‐flux analysis indicate the following. In the presence of Ca the permeabilities are approximately: Na (1.0 × 10−6 cm/sec); K (5.6 × 10−6 cm/sec); Cl (1.4 × 10−6 cm/sec). Upon Ca removal the K and Cl permeabilities are not significantly altered. However, there is an approximately four‐fold increase in Na permeability (4.5 × 10−6 cm/sec). This increase explains the observed depolarization in membrane potential upon Ca removal. It has been suggested previously that Ca may regulate the in vivo depolarization observed during transition from oocyte to ovulated egg in the amphibian. The present experiments indicate that, if Ca does play a role, its role is not analogous to the in vitro effect on the oocyte, since the ovulated egg has reduced Na as well as K permeability.

The electrical potential difference across the cell membrane of heart muscle. Biophysical considerations.

The electrical potential difference across the cell membrane of heart muscle cells is a diffusion potential arising from the interaction of fixed charges within the membrane pores with NaCl and KCl diffusing into and out of the cell. The magnitude and sign of this potential difference depend on the relative permeabilities, of the membrane to K, Na, and Cl. The resting membrane is predominantly permeable to K, while the action potential is characterized by a transient increase in Na permeability. An intracellular solution of high K concentration and low Na concentration is separated by the cell membrane from an extracellular solution having a low K concentration and a high Na concentration. These concentration differences are maintained by active transport processes that utilize the energy derived from cellular metabolic reactions to transport Na and K "uphill" against electrical and concentration gradients.

Fibrillation and Potassium Influx

Absolute influx and efflux of potassium-42 have been measured in isolated rabbit atria during acetylcholine-induced fibrillation. The efflux of potassium was increased three to four times; influx was not changed. The data are interpreted as indicating that an inhibition of active K uptake is not involved in the initiation of fibrillation, and that the process results from a marked increase in Na permeability.

Fibrillation and Potassium Influx

Absolute influx and efflux of potassium-42 have been measured in isolated rabbit atria during acetylcholine-induced fibrillation. The efflux of potassium was increased three to four times; influx was not changed. The data are interpreted as indicating that an inhibition of active K uptake is not involved in the initiation of fibrillation, and that the process results from a marked increase in Na permeability.