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Is inward calcium current in crayfish muscle membrane constituted of one or two components?

Two inward currents were observed in crayfish muscle membrane during depolarization steps by the method described by Adrian et al. (1970). Under voltage clamp conditions, hyperpolarization steps elicited a large current (leak current If), associated with an inward voltage dependent current. This inward current was inhibited by niflumic acid (NA), a drug known to block Cl---HCO-3 exchange (Cousin et Motais 1982; Brûlè et al. 1983b). Dynamic outward currents triggered by depolarizing steps were inhibited to a great extent by TEA, the not inhibited portion disappearing when procaine (2 mmol/l) was added to external solution. In the presence of TEA, procaine and NA, it was thus possible to dissect the regenerative calcium current (ICa) into two components: a "fast component" (ICa1) and a "slow component" (ICa2). The reversal potential of ICa was 65 mV (for [Ca]0 = 2.8 mmol/l), and [Ca]i could be calculated to be 1.6 X 10(-5) mol/l. This value of [Ca]i is the same as calculated from values reported by Hencek and Zachar (1977). ICa1 was triggered at a threshold membrane potential of -45 mV and ICa2 at -30 mV. Moreover, the inactivation kinetics for ICa1 was faster than that for ICa2. Our results are in perfect agreement with those obtained by Zahradník and Zachar (1982) who postulated two populations of calcium channels.

Animals↗

[Conjugation components in alpha-adrenergic reactions in smooth muscles].

Changes in the electric and mechanical activity conditioned by norepinephrine in the deferent duct, musculus rectococcygeus, aortic band and the portal vein in rats, as well as influence exerted on these changes by the replacement of Na+ ions with NH4+ ones, by the action of novocain (1-10(-3) g/ml), strophanthin (1-10(-5) g/ml), excess (25 mM) and deficiency (0.25 mM) of Ca2+ ions and by that of manganese chloride (2 mM) and lanthanum (1 mM) were analyzed. As evidenced, the basic mode of conjugation in alpha-adrenergic reactions is an intensified supply of Ca2+ ions to the cells, unattended by any changes in the degree of the membrane potential at rest. Depolarization and quickened generation of action potentials occur in musculus rectococcygeus and in the portal vein, in the lastly named case -- under the effect of high norephrine concentrations (10(-6)-10(-5) g/ml).

Animals↗

Electrical membrane properties of the muscle lamellae in Branchiostoma myotomes.

The membrane characteristics of amphioxus myotome cells were investigated using the chopped-current clamp method. The extremely thin myotome lamellae had a membrane resistance of 2.2 to 7.7 k omega cm2 and a capacity of 0.4 to 1.3 microF/micron2. The steady state current-voltage relation showed outward rectification. In Cl- - and Na+ -free solutions containing 400 mM TEA the input resistance and the time constant increased threefold and Ca2+ -dependent action potentials occurred, indicating the presence of a Ca2+ component in membrane current. It is discussed whether Ca2+ ions entering the cell during the normal action potential may significantly increase the intracellular free Ca2+ concentration.

Action Potentials↗

Potassium-induced relaxation of the rat anococcygeus muscle.

The nature of K-induced relaxations of the isolated rat anococcygeus muscle was studied in Tyrode's solution containing a variety of smooth muscle stimulants. When the tone of the preparation was raised by ACh (1 X 10(-6) M), the inhibitory responses to excess K (20-50 MM) were almost completely prevented by tetrodotoxin (1 X 10(-6) M) but not affected by ouabain (2 X 10(-4) M). When the preparation was contracted by barium (5 X 10(-3) M), tetraethylammonium (3 X 10(-2) M) or procaine (8 X 10(-3) M), relaxations by excess K (10-60 mM) were not affected by tetrodotoxin but completely inhibited by ouabain. It is concluded that two types of K-induced relaxations can occur depending on the smooth muscle stimulant used for elevating the tone of the preparation: the one is due to an activation of the electrogenic Na pump mediated by Na+, K+ ATPase of the smooth muscle membrane, the other is due to a stimulation of the inhibitory nerves by K.

Animals↗

[The characteristics of drug distribution in the body under the influence of different types of electrical current].

Rabbit experiments showed that distribution of drugs in the body in intratissue electrophoresis is related to current type. The drugs reach the target organ and are deposited best under the influence of sinusoidal modulated and galvanic currents. The experiments' evidence may serve the basis for differential use of electric currents for intratissue electrophoresis.

Anesthetics, Local↗

Combination of cisplatin-procaine complex DPR with anticancer drugs increases cytotoxicity against ovarian cancer cell lines.

DPR, cis-diamminechloro-[2-(diethylamino)ethyl 4-amino-benzoate, N4]-chlorideplatinum(II) monohydrochloride monohydrate, is a newly developed water-soluble platinum compound which possess minimal cross-resistance to cisplatin and shows relatively less side effects. In an attempt to establish whether the combination of DPR with other conventional anticancer drugs would be of any benefit we assessed in vitro the cytotoxic effects of combinations of DPR with the antimetabolites 5-fluorouracil (5-FU) and methotrexate (MTX), the alkylating agents mitomycin C (MMC) and cisplatin, the antimicrotubule agent taxol (TAX), and the intercalating agent of the anthracycline group doxorubicin (DOX) on murine M5076 ovarian reticulosarcoma and human A2780 ovarian carcinoma cells. These agents were selected because of their common use in the clinic and because they represent four distinct categories of antineoplastic mechanisms. Cells were incubated for 72 h in the presence of single or combined drugs, and the cytotoxic effect was determined by the MTT assay. The analysis of combination treatment was made by the isobole method. In human A2780 cells, an overall synergy was found for DPR combined with 5-FU, DOX and cisplatin. Synergistic effects were also observed for most combinations with MTX or MMC. A DPR concentration-dependent additivity and antagonism was seen at the highest MTX concentration (1 microM), while additive effects were observed for the combined treatments of DPR and low concentrations of MMC (0.008 and 0.0016 microM). Additive effects were also observed for the association of DPR and TAX over most combinations tested. In murine M5076 cells, synergism was the prevailing result observed when DPR was combined with 5-FU, DOX, MMC or cisplatin. When administered together with MTX we observed additivity over most combinations tested. These findings suggest that DPR, when simultaneously administered with standard anticancer agents, may be advantagious for cytokilling.

Antibiotics, Antineoplastic↗