Effects Of Extracellular Cations Research Articles

Effect of extracellular cations on the chemotherapeutic efficacy of anticancer drugs.

Cancer development and the efficiency of chemotherapy relies on the patients calcium-related pathological status such as hyper- or hypocalcemia. In the present study, we investigated the effect of extracellular cations such as calcium and magnesium on the therapeutic efficacy of antitumor drugs. The analytic parameters used were cellular drug uptake/excretion and the chemosensitivity of the human breast cancer cell lines, MCF7 and MCF7/ADR. Both calcium and magnesium ions decreased the membrane permeability of cancer cells, which was determined by cell size analysis. These divalent ions also lowered the drug uptake and the cytoplasmic levels of rhodamine 123 and adriamycin, suggesting that they might interfere with the diffusion of these drugs by modifying the physical properties of the cytoplasmic membrane. The acute cytotoxicity of adriamycin after a short period of incubation correlated with changes in its cytoplasmic level. Our results indicate that these extracellular cations might play an important role in the therapeutic activities of anticancer drugs in cancer patients. These results also provide insight a new aspect of chemotherapy, because they suggest that the therapeutic doses of anti-cancer drugs should be modified in cancer-bearing patients presenting with abnormal blood calcium levels.

Effect of extracellular cations on the inward rectifying K+ channels Kir2.1 and Kir3.1/Kir3.4

The effects of Ba2+, Mg2+, Ca2+ and Na+ as blocking ions were investigated in 90 and 10 mM extracellular K+ solutions on the cloned inward rectifying K+ channel Kir2.1 expressed in Xenopus oocytes. Some data were also obtained using another inward rectifying K+ channel Kir3.1/Kir3.4. The addition of Ba2+ caused a concentration-, voltage- and time-dependent block of both channels. Decreasing the extracellular K+ concentration augmented the block. The data suggest that Ba2+ blocks the channels by binding to a site within the channel pore and that the electrical binding distance, δ, of the site is significantly different for Kir2.1 and Kir3.1/Kir3.4 (∼ 0·38 and ∼ 0·22, respectively). Mg2+ and Ca2+ caused an instantaneous concentration- and voltage-dependent block of both channels. With Kir2.1, decreasing the K+ concentration augmented the block. The voltage dependence of the block was less than that of Ba2+ (δ, ∼ 0·1), indicating a more superficial binding site for these ions within the channel pore. The affinity of the channels for Mg2+ and Ca2+ was ∼ 1000-fold lower than that for Ba2+. Addition of Na+ resulted in a concentration-, voltage- and time-dependent block of Kir2.1, similar to that observed with Ba2+. The competition between the blocking cations (for Kir2.1: Ba2+, Mg2+, Ca2+; for Kir3.1/Kir3.4: Ba2+) and extracellular K+ suggests that the binding sites for the blocking cations may be sites to which K+ binds as part of the normal passage of K+ through the channels. It is possible that under normal physiological conditions naturally occurring extracellular cations may partly block the two inward rectifying K+ channels.

Effects of extracellular cations on translation in poliovirus-infected cells.

The effect of pH and different concentrations of added monovalent and divalent cations on translation in poliovirus-infected HeLa cells has been examined. A strong effect on protein synthesis was observed when the concentration of sodium ions was modified. If cells were placed in a hypotonic medium after virus adsorption, no shut-off of cellular translation took place, nor were viral proteins synthesized. An increase in the multiplicity of infection partially overcame this effect. Reversal of the shut-off of cellular translation and inhibition of viral protein synthesis was achieved when cells were placed in hypotonic medium 2 h after infection. Modification of divalent cations (calcium or magnesium) had little or no effect on the pattern of translation. On the other hand, acidic pH (below 6) inhibited both cellular and viral protein synthesis, whereas basic pH had no influence. During infection the synthesis of poliovirus proteins reached a maximum at about 4 to 6 h and then declined. This inhibition of viral translation was partially prevented if cells were placed in a medium containing a high concentration of potassium although the cytopathic effect was prevented. These results indicate that viral protein synthesis and the cytopathic effect were, to a large extent, influenced by the external monovalent ion concentration.

Effects of extracellular cations and energy substrates on the acrosome reaction of precapacitated guinea pig spermatozoa

AbstractIt is well established that extracellular Ca2+ and an alkaline pH are essential for the acrosome reaction of precapacitated guinea pig spermatozoa. In the present study, we investigated how other extracellular cations (Na+, K+, and Mg2+) and energy substrates (glucose, lactate, and pyruvate) affect the acrosome reaction of these spermatozoa. The effect of osmolality of the medium on the reaction was also examined.It was found that precapacitated spermatozoa could undergo the acrosome reaction in a medium with an osmolality of as low as 160 mOsmol or as high as 500 mOsmol. However, the osmolality range within which large proportions of spermatozoa underwent the acrosome reaction while retaining strong motility was 220 to 380 mOsmol. Extracellular Na+ was essential for the reaction to occur. A few spermatozoa could acrosome react in a medium with a very low concentration of Na+ (5 mM or less), but a higher concentration of Na+ (more than 60 mM) was needed to ensure the acrosome reaction in the majority of spermatozoa. High concentrations of extracellular K+ were not essential for the reaction, but the presence of K+ at physiological level ensures that the reaction will occur consistently at a high rate. Extracellular Mg2+ was not required for the acrosome reaction. The high concentrations of Mg2+ (up to 20 mM) and K+ (up to 60 mM) that were tested did not affect the incidence of the acrosome reaction. Exogenous substrates were not essential for the reaction. Although the majority of precapacitated spermatozoa could acrosome react in substrate‐free medium, the presence of substrates in the medium, particularly that of pyruvate, seemed to be beneficial to the reaction.

Effects of extracellular cations and ouabain on catecholamine-stimulated sodium and potassium fluxes in turkey erythrocytes.

In turkey erythrocytes, potassium influx can be inhibited by several cations whose order of effectiveness is Rb greater than Cs greater than Li greater than Mg = Ca = Ba. Extracellular sodium does not alter potassium influx. Sodium influx is not altered by any of these monovalent cations but magnesium, calcium, or barium reduced sodium influx by 30 to 40%. Potassium outflux is not influenced by extracellular sodium or potassium while sodium outflux is not influenced by extracellular potassium but increases progressively with increasing extracellular sodium. Isoproterenol stimulates potassium influx only when sodium or lithium is present in the medium and catecholamine stimulation increases progressively with increasing extracellular sodium. Isoproterenol-stimulated sodium influx is enhanced by extracellular potassium, rubidium or cesium, and catecholamine stimulation increases progressively with increasing extracellular potassium. Isoproterenol inhibits potassium outflux in a solution free of sodium and potassium, and this inhibition can be abolished by adding sodium but not by adding potassium. In solutions containing both sodium and potassium, isoproterenol stimulates potassium outflux, and this stimulation increases progressively with increasing extracellular sodium or potassium. Isoproterenol-stimulated sodium outflux is not influenced by extracellular sodium or potassium. Isoproterenol-stimulated cellular cyclic adenosine 3':5'-monophosphate (cyclic AMP) is reduced slightly (25%) by removing extracellular sodium and potassium from the incubation solution, but this effect is not of sufficient magnitude to account for the effects of these cations on isoproterenol-stimulated cation transport. Ouabain does not alter the effect of extracellular sodium or potassium on isoproterenol-stimulated potassium influx; however, the glycoside potentiates (by 20 to 40%) the effects of these two cations on isoproterenol-stimulated sodium influx. Ouabain does not alter potassium outflux when the incubation solution contains both sodium and potassium; however, ouabain stimulates potassium outflux in an incubation solution free of sodium or potassium.