Biomedical subjects

S Hering

Publications and source records attributed to S Hering.

96 records · Page 6Linked to original sources

PubMed1983

Sodium current in freshly isolated and in cultured single rat myocardial cells: frequency and voltage-dependent block by mexiletine.

Effects of mexiletine on the rapid inward sodium current (INa) were studied in freshly isolated single cells of the ventricular myocardium of adult rats and in single cultured ventricular muscle cells of newborn rats. The current was measured in internally perfused, voltage-clamped cells by a single suction pipette technique. Mexiletine was applied extracellularly. INa was reduced by the drug in both preparations when the membrane was depolarized to -20 mV by short (8 ms) pulses delivered at a frequency of 0.1 Hz from a holding potential of -100 mV. Mexiletine in a concentration of 50 microM diminished the INa under this condition by 70 +/- 8% (mean +/- S.D.) in the adult myocardial cells. A nearly equal reduction of the current (65 +/- 10%) was caused in the neonatal myocardial cells by 15 microM mexiletine. A use-dependent block of INa was produced in the presence of 10 and of 20 to 30 microM mexiletine, respectively, in the neonatal and the adult myocardial cells by repetitive depolarizing test pulses applied at frequencies between 1 and 7 Hz. Prolongation of the pulse duration from 10 to 100 ms enhanced the use-dependent block of INa in both preparations. The frequency-dependent action of mexiletine could be modulated by 100-ms hyperpolarizing prepulses from -80 to -140 mV. The time course of the use-dependent block (prepulse off) and unblock (prepulse on) was monitored. The slope of the inactivation curve of INa in the neonatal heart cells was reduced in the presence of mexiletine and the midpoint of the curve was shifted in the hyperpolarizing direction. These findings are interpreted as suggesting that binding of mexiletine to the sodium channel of the rat myocardial cells studied is enhanced when the cell membrane becomes depolarized.

Aging↗

PubMed1983

Migration of K562 cells and its inhibition by lymphokines.

Cells of the human myelogenous line K562 migrate from glass capillaries to the glass or plastic surface of culture flasks in the presence of RPMI 1640. Like macrophages they form a halo around the opening of the capillary. Migration is inhibited by lymphokine-containing supernatants from mixed lymphocyte culture (MLC). Concanavalin A stimulated lymphocytes and from several cell lines.

Animals↗

PubMed1982

Characterization of the fast sodium current in isolated rat myocardial cells: simulation of the clamped membrane potential.

1. The fast sodium inward current of freshly isolated single rat myocardial cells was studied by means of the internal perfusion-voltage clamp method. 2. The voltage dependence of this current did not differ from the current-voltage characteristics of the fast sodium inward current described for other excitable cells and tissues. 3. The time constant of inactivation of the Na+ current of the isolated myocardial cells ranged between 5.2 msec at -58 mV and 0.5 msec at +18 mV. The activation time constant ranged from 0.3 msec at -55 mV to 70 microseconds at +10 mV. 4. The reactivation time constant of the maximum sodium current at a holding potential of -100 mV was found to be 21 +/- 5 msec. 5. A mathematical model was developed for the simulation and analysis of the influence of the series and shunt resistances on the time response of the membrane potential. The results of the modelling make it clear that control of the series and shunt resistances in any given experiment is a conditio sine qua non for a valid analysis of the kinetic parameters of the sodium inward current. 6. Sodium currents with delayed activation kinetics must be regarded as an indication of insufficient control of the membrane potential.

Animals↗

PubMed1980

Voltage clamp method on single cardiac cells from adult rat heart.

Voltage clamp experiments on isolated cardiac cells from adult rat hearts were carried out using an intracellular dialysis method. The fast inward current was recorded. Tetrodotoxin (TTX) at a concentration of 2.5 x 10(-7) g/ml blocked this current to 30% of its initial value. Inward maximal fast current density was calculated to be 0.14--0.7 mA/cm2.

Animals↗

PubMedDate not supplied

Use- and voltage-dependent depression by ethmozine (moricizine) of the rapid inward sodium current in single rat ventricular muscle cells.

Effects of ethmozine (moricizine) on the rapid inward sodium current (INa) were studied in freshly isolated single cells of rat ventricular myocardium. INa was measured by means of a patch clamp method for observing integral ionic currents. Ethmozine was applied extracellularly to a small cell membrane patch at concentrations of 10, 20, and 40 microM. At a stimulation frequency of 0.1 Hz the drug decreased the peak INa without producing a shift of the current-voltage curve, but shifted the V0.5 of the steady-state inactivation curve by -6 mV. At frequencies of 2-5 Hz the ethmozine-induced block exhibited a prominent use dependence, with trains of depolarizing clamp pulses 5-50 ms in duration eliciting maximal INa from holding potentials at which the steady-state inactivation variable h infinity was close to 1. The use-dependent inhibition of INa became more pronounced with an increase in both stimulation rate and pulse duration. In contrast to what has been observed in the node of Ranvier of the frog, the present results indicate that ethmozine binds to both inactivated and open Na+ channels, but that the contribution of the open channel block to the overall block at depolarizing clamp step durations of several hundred milliseconds is small in comparison with the contribution of the block of inactivated channels.

Animals↗

PubMedDate not supplied

X chromosomal and autosomal loss of heterozygosity and microsatellite instability in human cervical carcinoma.

The study analyzes tumor material and normal tissue from 27 patients with pure squamous cell carcinoma of the uterine cervix for loss of heterozygosity (LOH) and microsatellite instability (MSI) on 14 autosomal and 11 X chromosomal loci. Overall, 4-40% of the informative cases showed LOH at autosomal regions with the highest frequency at 3p (21-40%) and a marked frequency at 2q35-q37.1 (12.5%) and 17p13.3 (10%), representing regions with putative tumor suppressor gene (TSG) function. The frequency of X chromosomal LOH ranged from 4% to 20%, with a maximum at Xq28 (20%) and Xq11.2-q12 (17%), again indicating alterations in TSG. A 12% LOH was seen at Xq21.33-q22.3, a region encoding a protein with a regulatory function in the cell cycle via cyclin-dependent kinases. MSI was detected in autosomal regions in up to 7% in regions linked to the X chromosome in up to 11%, probably indicating alterations of mismatch repair mechanisms. Our results and those obtained from the literature suggest that autosomal LOH and MSI in carcinomas of the cervix uteri are predominantly found at regions with putative TSG function. Beside TSG alterations, X chromosomal LOH is probably more strongly connected to disturbances in cell cycle regulation.

Carcinoma↗