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Biomedical subjects

K F Schmidt

Publications and source records attributed to K F Schmidt.

30 records · Page 2Linked to original sources

Effect of intracellularly applied sodium ions on the dark voltage of isolated retinal rods.

Isolated retinal rods of the frog consisting of the outer segment and the ellipsoid were patch-clamped and recorded in the whole-cell mode. The recording pipettes were filled with solutions of different composition in order to alter the cytoplasmic content of sodium, phosphate, and calcium ions, and guanine nucleotides. When a simple medium with potassium as the principal cation was used, the dark voltage slowly approached more negative values. This tendency of spontaneous hyperpolarization was reduced significantly when cGMP or GTP were present in the pipette medium. Sodium ions, on the other hand, clearly increased the speed of hyperpolarization. In the presence of sodium (20 mM), the stabilizing effect of GTP did not occur and that of cGMP was clearly diminished. Phosphate (20 mM) neutralized the sodium effect. High calcium levels (100 microM) did not measurably influence the time course of hyperpolarization. We conclude that the normal cytoplasmic sodium level in rods does not exceed 10 mM and that higher internal sodium concentrations interfere with the sodium-calcium exchange mechanism.

Animals↗

Dopamine modulates the kinetics of ion channels gated by excitatory amino acids in retinal horizontal cells.

Upon exposure to dopamine, cultured teleost retinal horizontal cells become more responsive to the putative photoreceptor neurotransmitter L-glutamate and to its analog kainate. We have recorded unitary and whole-cell currents to determine the mechanism by which dopamine enhances ion channels activated by these agents. In single-channel recordings from cell-attached patches with agonist in the patch pipette, the frequency of 5- to 10-pS unitary events, but not their amplitude, increased by as much as 150% after application of dopamine to the rest of the cell. The duration of channel openings also increased somewhat, by 20-30%. In whole-cell experiments, agonists with and without dopamine were applied to voltage-clamped horizontal cells by slow superfusion. Analysis of whole-cell current variance as a function of mean current indicated that dopamine increased the probability of channel opening for a give agonist concentration without changing the amount of current passed by an individual channel. For kainate, noise analysis additionally demonstrated that dopamine did not alter the number of functional channels. Dopamine also increased a slow spectral component of whole-cell currents elicited by kainate or glutamate, suggesting a change in the open-time kinetics of the channels. This effect was more pronounced for currents induced by glutamate than for those induced by kainate. We conclude that dopamine potentiates the activity of horizontal cell glutamate receptors by altering the kinetics of the ion channel to favor the open state.

Analysis of Variance↗

Effect of guanine nucleotides on the dark voltage of single frog rods.

Single frog rods consisting of the outer segment and the ellipsoid were investigated by the whole-cell patch-clamp technique. When the recording pipette was filled with a simple intracellular medium containing potassium as the principal cation, a slow increase in dark voltage (hyperpolarization) associated with a decay of the photoresponses was observed. The hyperpolarization started at a dark voltage of -27 +/- 8 mV, followed an exponential course, and leveled out at -52 +/- 6 mV. The time constant was proportional to the access resistance of the preparations. With a pipette medium containing a 0.5 or 1.0 microM cGMP, the initial dark voltage was shifted to more positive values and the tendency of hyperpolarization was clearly attenuated. Similar results were obtained with 1 mM GTP. The effects of GDP and of ATP were less significant. In experiments with 1 mM GTP plus 1 mM ATP, the dark voltage behaved as in experiments with only GTP. The stabilizing action of GTP was amplified by EGTA so that with 1 mM GTP plus 1 mM free EGTA the dark voltage was stable at a level of -15 mV. It is concluded that the preparations lose intracellular components such as cGMP and GTP by diffusion into the recording pipette and that the losses are prevented or reduced when the pipette medium contains these nucleotides in nearly physiological concentrations. For the internal transmitter cGMP, the results suggest that its free concentration does not exceed 1 microM.

Adenosine Triphosphate↗

Effect of gangliosides on nerve regeneration in rats.

The objective of the study was to investigate the effects of gangliosides on the regeneration of the sciatic nerve after a crush injury in the rat. After a temporary complete interruption of axonal conduction, nerve conduction velocity was again measurable on the 13th day. On that day and at all subsequent measuring times, the conduction velocity of the damaged nerves was greater in the ganglioside-treated rats than in the control animals which were treated only with the solvent and reached significant values on day 15 and 18.

Action Potentials↗

[Intensive supervision of labor with the help of the computor (author's transl)].

A system of supervision which we developed was described. With this system it is possible to make on-line evaluations of the CTG and postpartal blood analyses from the cord blood via computors (AEG 60-10 and AEG 60-50). The computed parameters together with all obstetrical data collected during the pregnancy (results from ultrasonic tests, estrogen and HPL analyses, anamnestic data and additional "clinical findings") as well as off-line evaluated CTG findings made during the course of the pregnancy were scored. The CTG is evaluated on-line via the "cross correlation function" and can be produced in a wide variety of parameters at any time during labor. The complete system is demonstrated on the basis of an individual case analysis. The first statistical individual case analyses of deceleration in CTG were compared with the classical Hon and Caldeyro-Barcia method of calculation.

Diagnosis, Computer-Assisted↗

Horizontal cell glutamate receptor modulation by NO: mechanisms and functional implications for the first visual synapse.

Neurons of the horizontal cell retinal neural network are subject to modulation by the neurotransmitter nitric oxide (NO). We have examined the effects of NO on glutamate receptor function in isolated horizontal cells from the perch (Perca fluviatilis) using the concentration ramp technique to simultaneously record receptor current and agonist concentration. Dose-response curves for glutamate (0-1 mM) and kainate (0-200 microM) were measured in the presence and absence of 1-2 mM sodium nitroprusside (SNP), 1 mM 8-Br-cGMP, 100 microM cyclothiazide or 200 microM dopamine as modulators. SNP increased the EC50 (i.e. decreased affinity) for glutamate and increased Imax (i.e. increased efficacy), whereas 8-Br-cGMP increased EC50, but not Imax. In the presence of the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) receptor desensitization blocker cyclothiazide, the SNP-induced increase in EC50 persisted, but the increase in Imax was blocked. The increase in EC50, but not the increase in Imax was also observed when the non-desensitizing agonist kainate (100-200 microM) was applied in the presence of SNP. When 2 mM SNP and 200 microM dopamine were applied together, they increased Imax (740 vs. 2455 pA) and EC50 (422 vs. 682 microM). Our findings indicate that NO modulates horizontal cell glutamate responses by reducing the affinity of receptors for glutamate while simultaneously increasing the maximal current. The shift in affinity is cGMP-mediated and independent of desensitization. The action of NO on horizontal cell glutamate receptors is distinct from, but synergistic with. that of dopamine. Glutamate receptor modulation by NO qualitatively predicts the action of NO on horizontal cell light responses in situ and may alter transmission at visual synapses according to adaptational conditions.

Animals↗