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PubMed1989

Ionic currents in single smooth muscle cells from the ureter of the guinea-pig.

1. Ionic currents underlying the action potential were recorded from enzymatically isolated smooth muscle cells of guinea-pig ureter. 2. The action potential recorded from a single cell was similar to that from a multicellular preparation. It showed repetitive spikes on a plateau potential which followed the first spike. Treatment with 10 mM-tetraethylammonium (TEA) increased the amplitude and duration of the plateau phase and abolished the repetitive spikes. 3. Under voltage clamp mode, at least two (maybe three) kinds of outward currents were activated during depolarizing pulses. The main outward current was Ca2+-dependent K+ current (IK(Ca], which was mostly blocked in Ca2+-free solution, or by application of 1 mM-cadmium (Cd2+) or 2 mM-tetraethylammonium (TEA). IK(Ca) was greatly decreased by treatment with 5 mM-caffeine or an addition of 10 mM-EGTA in a pipette solution. 4. In the presence of 1 mM-Cd2+ and 2 mM-TEA, a small transient outward current remained. 4-Aminopyridine (1 mM) suppressed the transient outward current by about 40%. Time- and voltage-dependent delayed rectifier outward currents were small in ureter cells. An inwardly rectifying K+ current was not detected. 5. An application of 1 mM-Cd2+, 5 mM-cobalt (Co2+), 1 mM-lanthanum (La3+) or 0.1 microM-nifedipine completely blocked the action potential. Replacement of 80-90% of extracellular Na+ with Li+ or Tris almost abolished the plateau potential and repetitive spikes but did not change significantly the first spike. 6. In the presence of 30 mM-TEA, the inward current elicited by depolarization was monophasic and lasted for more than 1 s. Application of 1 mM-Cd2+, 1 mM-La3+, 0.1 microM-nifedipine, or 5 mM-Co2+ completely blocked inward current. The replacement (87%) of extracellular Na+ ions with Li+, Tris, sucrose or TEA speeded up the decay of inward current; the inward current decreased by 10-60% at the end of a 500 ms pulse. 7. Even in low-Na+ solution (120 mM-TEA), the inactivation of ICa had a quite slow component (tau = 1 s), in addition to another faster component (tau = 100 ms) at 0 mV. When short depolarizing clamp pulses (50 ms) were repetitively applied at short intervals (50 ms) and with interpulse voltage of -10 or -20 mV to mimic the repetitive spikes on the plateau of the action potential, the decline of peak Ca2+ current during the train of pulses was smaller than the decay of Ca2+ current during a long pulse.(ABSTRACT TRUNCATED AT 400 WORDS)

4-Aminopyridine↗
PubMed1990

Ion selectivity of the Vibrio alginolyticus flagellar motor.

The marine bacterium, Vibrio alginolyticus, normally requires sodium for motility. We found that lithium will substitute for sodium. In neutral pH buffers, the membrane potential and swimming speed of glycolyzing bacteria reached maximal values as sodium or lithium concentration was increased. While the maximal potentials obtained in the two cations were comparable, the maximal swimming speed was substantially lower in lithium. Over a wide range of sodium concentration, the bacteria maintained an invariant sodium electrochemical potential as determined by membrane potential and intracellular sodium measurements. Over this range the increase of swimming speed took Michaelis-Menten form. Artificial energization of swimming motility required imposition of a voltage difference in concert with a sodium pulse. The cation selectivity and concentration dependence exhibited by the motile apparatus depended on the viscosity of the medium. In high-viscosity media, swimming speeds were relatively independent of either ion type or concentration. These facts parallel and extend observations of the swimming behavior of bacteria propelled by proton-powered flagella. In particular, they show that ion transfers limit unloaded motor speed in this bacterium and imply that the coupling between ion transfers and force generation must be fairly tight.

Cell Movement↗
PubMed1985

Contribution of myocardial diffuse double-layer calcium to contractile function.

The role of diffuse double-layer calcium in cardiac excitation-contraction coupling was examined using rabbit interventricular septa, cultured neonatal rat myocardial cells, and gas-dissected sarcolemmal membranes. The diffuse double layer refers to the space directly adjacent to the sarcolemma where the ionic composition of the media is a direct function of the membrane surface potential. The divalent cation dimethonium was used as a specific probe for the diffuse double layer. According to Gouy-Chapman theory, replacement of sodium with sucrose should increase the amount of calcium located in this compartment. Dimethonium (10 mM) was found to decrease calcium uptake and contractility during low-sodium (33 mM) perfusion when the perfusate contained sucrose but not LiCl. Dimethonium did not decrease calcium uptake or contractility during control perfusion. The results suggest that calcium present in the myocardial diffuse double layer can be augmented or reduced in accordance with Gouy-Chapman theory. Changes in diffuse double-layer calcium are accompanied by small (7.8%) but significant changes in contractility.

Animals↗
PubMed2002

Role of Ca(2+) in the synchronization of transmitter release at calyceal synapses in the auditory system of rat.

The synchronization of transmitter release in the synapse of the medial nucleus of the trapezoid body (MNTB) is achieved during early postnatal development as a consequence of elimination of delayed asynchronous releases and appears to reflect changes in the dynamics of Ca(2+) entry and clearance. To examine the role of Ca(2+) in regulating synchronization of transmitter release in the mature synapse (after postnatal day 9, P9), we perturbed Ca(2+) dynamics systematically. Replacement of external Ca(2+) (2 mM) with Sr(2+) induced delayed asynchronous release following the major EPSC. We tried to reproduce asynchronous releases without using Sr(2+) and instead by manipulating the time course and the size of Ca(2+) transient in the presynaptic terminal, under the assumption that replacement of external Na(+) with Li(+) or application of eosin-Y would prolong the lifetime of Ca(2+) transient by reducing the rate of Ca(2+) extrusion from the terminal. With application of Li(+), Ca(2+) transient in the terminal was prolonged, the EPSC decay time course was prolonged, and the EPSC amplitude increased. However, these EPSCs were not followed by delayed asynchronous release. When Ca(2+) influx was reduced, either by partial Ca(2+) channel blockade with a low concentration of Cd(2+) or omega-agatoxin IVA, a marked asynchronous release resulted. This was further enhanced by the combined application of Li(+) or eosin-Y. These results suggest that cooperative increases of both Ca(2+) influx and Ca(2+) clearance capacities leading to a sharper Ca(2+) spike in the presynaptic terminal underlie synchronized transmitter release in the presynaptic terminal of the MNTB.

Animals↗
PubMed1978

Comparative effects of dihydroergotoxine (DHET) on CBF and metabolism changes produced by experimental cerebral edema, hypoxia and hypertension.

Dihydroergotoxine (DHET) perfused in the dog (100 microgram/kg) presenting a cerebral per-hypocapno-anemic syndrome reduces cerebral hyperemia, increases cerebral venous PO2, despite the rise in CMRO2 and favors glucose oxidation by the brain. DHET (20 mg/kg p.o.) is able to drop mean, diastolic and systolic arterial blood pressures in renal-hypertensive rats having a cerebral edema induced by triethyltin intoxication without affecting cerebral water and sodium levels which are increased in the controls. DHET (50 microgram/kg i.v.) can also improve EEG changes produced by a traumatic edema but does not exert (200 microgram/kg i.v.) any effect on EEG changes produced in the rabbit by lithium chloride intoxication.

Anemia↗
PubMedDate not supplied

[An electromyographic method for determining the antihypoxic activity of preparations].

To measure drug antihypoxic activity, an electromyographic method was worked out. The main idea of the method is to estimate the influence of these substances on the amplitude of slow electric waves of smooth muscles on an isolated strip of rat small intestine in situ. This parameter whose value directly depends on tissue pO2 was recorded under the conditions of artificial ischemia of the intestinal strip. Circulatory hypoxia was simulated by the clamping of mesentery vessels, and the time was determined, during which the amplitude of slow electric waves reduced to 1/3 of the initial value in control animals and rats treated beforehand with the drugs under study. Antihypoxic activity of the drugs was calculated as difference in these time intervals between experiment and control, given in per cent.

Animals↗
PubMedDate not supplied

[The effect of lithium oxybutyrate on the circadian rhythms of the activity and body temperature of rats maintained under different light regimens].

The chronobiological properties of lithium hydroxybutrate were studied in the open field test at the preventive administration of the drug to rats (7 days, 10 mg/kg daily subcutaneously) kept under natural photoperiod of the summer and winter solstice and CT 12:12. It was found that lithium hydroxybutrate can preserve, reveal the lost rhythms and synchronize the available circadian and infradian rhythms of the activity and body temperature of the rats. The degree and direction of this effect depend on the initial rhythmostasis, the time of the drug administration and the regimen of illumination under which the animals are kept.

Animals↗
PubMed1990

Effects of drugs on blood-brain barrier permeability in rats chronically intoxicated by ethanol.

Male Wistar rats were divided in free choice conditions into heavy-drinkers consuming greater than 3.5 g/kg of ethanol daily (HD), and light-drinkers consuming less than 2.0 g/kg/day (LD). Subsequent 30 day intragastric administration of 25% ethanol (8-11 g/kg/day) caused an increase in permeability of the BBB to 14C-tyrosine, 14C-tryptophan and 14C-DOPA at all the stages of alcoholization. At late stages of intoxication (20-30 days) the penetration of horseradish peroxidase (HRP) indicating pinocytosis was present. All the changes were more pronounced in LD than in HD rats. Disulfiram, and to a lesser extent phenazepam and diazepam, when repeatedly injected (for 16-30 days) together with ethanol aggravated its effects. Clonidine and haloperidol antagonized ethanol-induced increase of the BBB permeability to labelled compounds and HRP in the two groups of rats. Picamilon, lithium oxybutyrate, chlorpromazine and alpha-tocopherol had little effect on the penetration of radioactive tracers but effectively antagonized the penetration of HRP. The other drugs were without effects on the BBB regulatory and barrier functions altered by chronic alcoholization. In view of the BBB dysfunction in chronic alcoholics the adequacy of the above-mentioned drugs for their treatment is discussed.

Alcohol Deterrents↗
PubMedDate not supplied

[Cardiotropic properties of lithium oxybutyrate in an experiment and in the clinic].

Lithium oxybutyrate was shown to exert pronounced coronarolytic effects, to increase volume velocity of the coronary blood flow, to improve blood supply to ischemic myocardial areas thereby providing oxygen reserve. Lithium oxybutyrate improves the functional state of the ischemic focus, limits zone of experimental myocardial necroses, exerts an antifibrillatory action, increases pain sensitivity threshold. A high efficacy of the drug was established during clinical study in patients with cardiac rhythm disorders.

Animals↗