Reduction Of Extracellular Na Research Articles

Does decreasing extracellular Na inhibit in vitro renin secretion by affecting NaCa exchange?

It has been shown previosly that in vitro renin secretion is inhibited by partial replacement of extracellular NaCl with either mannitol or choline chloride; the inhibitory effect is attributed to an increase in intracellular Ca, resulting from a decreased rate of Ca efflux via NaCa exchange. In the present experiements, we confirmeed that partially replacing NaCl with choline chloride inhibited renin secretion from rat renal cortical slices, but we found that atropime completely blocked the effect, suggesting cholinergic mediation. Partially replacing NaCl with mannitol also inhibited renin secretion, but the effect could not be attributed specfically to a reduction in extracellular Na. Moreover, the stimulatory effect of Ca chelation on renin secretion was antagonized by either mannitol- or choline chloride - containing incubation media. These results do not support the hypothesis that lowering extracellular Na inhibits renin secretion by a mechanism involving decreased Ca efflux via NaCa exchange.

Effects of rapid cooling on mechanical and electrical responses in ventricular muscle of guinea-pig.

The effect of rapidly lowering bathing solution temperature from 36.5 +/- 0.5 degrees C to various low temperatures was examined in guinea-pig ventricular muscle to explore the possible role of intracellular Ca2+ store sites in excitation-contraction coupling. Rapid cooling from 36.5 +/- 0.5 degrees C to below 18 degrees C caused contracture (rapid cooling contracture, r.c.c.) with subthreshold depolarization for contraction, if electrical stimulation was applied before cooling. R.c.c. peak tension depended on cooling temperature, and pre-cooling stimulation frequency and duration. R.c.c. induced after pre-cooling stimulation was enhanced by increased extracellular Ca2+ ( [Ca2+]o) and decreased by reduction of [Ca2+]o. Co2+ (2-4 mM) added to the HEPES-buffered Krebs solution, which suppressed the action potential plateau and inhibited twitch response, did not abolish r.c.c. after pre-cooling stimulation at high frequency. Reduction of extracellular Na+ concentration ( [Na+]o) before cooling enhanced r.c.c., and even in non-stimulated preparations, incubation in low [Na+]o below 68.8 mM for 20 min produced r.c.c. R.c.c. was superimposed on the tonic component of the K+ contracture, after a quiescent preparation has been depolarized beyond -40 mV by addition of solid KCl to normal Krebs solution. The relation between r.c.c. tension and membrane potential was shifted to the left along the voltage axis by reducing [Na+]o and shifted to the right by decreasing [Ca2+]o. Results suggest that well-developed intracellular Ca2+ store sites could sequester enough Ca2+ to generate tension by an energy-dependent process which had been loaded mainly by a voltage-dependent Na+-Ca2+ exchange mechanism and Ca2+ current, and that rapid cooling could cause Ca2+ release from the intracellular store sites with little contribution to membrane excitation in the guinea-pig ventricular muscle.

Effects of sodium substitutes on transient inward current and tension in guinea-pig and ferret papillary muscle.

We used ouabain-treated guinea-pig and ferret papillary muscles to study transient inward current (Iti), after-contractions, and tonic tension development during voltage-clamp pulses. Li, sucrose and choline were used isosmotically as Na substitutes to evaluate the effect of altering the Na equilibrium potential. We were unable to detect outward Iti at any potential up to +30 mV in normal or Na-depleted solutions. However, reduction of Na had a biphasic effect on Iti, initially increasing it and then reducing it at all clamp potentials from -50 to +20 mV. After-contractions were also initially increased and, in sufficiently Na-depleted solutions, decreased by reduction of extracellular Na. However, the peak in the after-contraction always occurred later than the increase in Iti and frequently coincided with the maximum suppression of the current. Complete suppression of after-contractions was not often achieved and always required more complete Na replacement than Iti suppression. Tonic tension responses were reduced by Na replacement, usually in synchrony with the reduction of Iti. The responses of Iti to Na replacement are consistent with a model of electrogenic Na-Ca exchange over the potential range positive to -50 mV. The responses deviate from the predictions of the model at more negative potentials. The results are consistent with the previous proposal that oscillatory changes in internal free Ca concentration underlie both Iti and after-contractions.

Alteration of transmembrane sodium and potassium gradients inhibits the action of luteinizing hormone in the luteal cell.

To evaluate the role of transmembrane ion flux on the acute response of luteal cells to LH, the effects of two drugs, ouabain and monensin, and changes in ion composition of the medium were examined. Ouabain, an inhibitor of the Na+ extrusion pump, and monensin, a selective Na+ ionophore, would be expected to increase the intracellular level of Na+. Both drugs produced a highly significant, dose-related and Na+-dependent inhibition of LH-stimulated cAMP accumulation and progesterone secretion. The IC50 values for ouabain and monensin for both responses to LH were about 50 and 0.1 microM, respectively, and inhibition of cAMP accumulation was competitive [inhibitory constant (Ki) = 20 and 0.06 microM, respectively]. Both drugs showed inhibition only in the intact cell, and no nonspecific cytotoxic effects were evident. No effect on the specific binding of gonadotropin or on LH-stimulated adenylate cyclase activity in membranes was seen, nor was inhibition reduced by coincubation of the cells with isobutyl methylxanthine, a cAMP phosphodiesterase inhibitor. Both drugs inhibited (Bu)2cAMP-stimulated progesterone accumulation. No effect of ouabain was seen on cholera toxin- or forskolin-stimulated cAMP accumulation, whereas monensin significantly inhibited this response to both agonists. Preincubation of cells with LH protected against inhibition of cAMP accumulation by ouabain and monensin. Removal of extracellular Na+ completely prevented inhibition by both drugs and slightly blunted the response to LH alone. However, reduction of extracellular Na+ from 128 to 32 mM, treatment of cells with tetrodotoxin (a sodium channel blocker), or increasing extracellular K+ from 5.4 to 66 mM had no effect on the stimulation of cAMP accumulation by LH. On the other hand, removal of extracellular Ca2+ completely blocked inhibition of LH-stimulated cAMP accumulation by ouabain or monensin. It is concluded that ouabain and monensin inhibit the acute stimulation of cAMP accumulation by LH probably as a result of an influx of Na+ into the luteal cell. The increase in intracellular Na+ does not appear to directly inhibit LH-sensitive adenylate cyclase activity, but induces a secondary influx of extracellular Ca2+ which inhibits activation of adenylate cyclase by LH at a site involved in coupling of the receptor to the enzyme. Luteal regression may be initiated by mechanisms similar to that caused by ouabain and monensin, because the characteristics of inhibition by these drugs is identical to that caused by prostaglandin F2 alpha, a physiological luteolysin.(ABSTRACT TRUNCATED AT 400 WORDS)

Experimental study of the conducted action potential in cardiac Purkinje strands

Conduction velocity is a complex physiological process that integrates the active and passive properties of the excitable cell. The relations between these properties in determining the conduction velocity are not intuitively obvious, and models have been used frequently to illustrate important relationships. To study the relationships of important parameters and to evaluate commonly used models, we changed conduction velocity experimentally in sheep cardiac Purkinje strands by reducing extracellular Na systematically. Cable analyses were also performed to obtain passive membrane and cable properties. Resting membrane resistance and capacitance did not change, nor did core resistance. Active properties measured in addition to conduction velocity included maximal upstroke velocity, action potential height, time constant of the foot, peak inward current, and upstroke power. With reduction in extracellular Na, all of these parameters of the action potential changed nonlinearly and not in direct proportion to the change in conduction velocity. The only simple relation found was a linear relationship between maximal upstroke velocity and peak inward current, normalized by the capacity of the foot. Models based on the cable equation and the wave equation offer a basis for quantitative analysis of conduction, and these data can be used to test the models.

Stimulus-secretion coupling in the rat lacrimal gland.

The role of calcium in stimulus-secretion coupling in the lacrimal gland was investigated. Rat exorbital lacrimal gland slices released peroxidase into the incubation medium after muscarinic or alpha-adrenergic receptor stimulation. In both cases, secretion appeared to involve exocytosis as revealed by electron microscopy. Secretion due to the muscarinic agonist carbachol was inhibited by Ca omission and by lanthanum. Secretion due to the alpha-adrenergic agonist phenylephrine was inhibited by Ca omission at 10(-5) M concentration but not at 10(-4) M concentration. The effects of 10(-4) M phenylephrine could be blocked by lanthanum or by reduction of extracellular Na. Both agonists stimulated 45Ca efflux, but phenylephrine was less efficacious. These results suggest that the agonists may cause exocytosis by stimulating influx of Ca or release of cellular Ca. Sodium may play a role in the Ca-release mechanism.