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Biomedical subjects

E Ficker

Publications and source records attributed to E Ficker.

34 records · Page 2Linked to original sources
PubMed1994

Gating of inwardly rectifying K+ channels localized to a single negatively charged residue.

Inwardly rectifying K+ channels (IRKs) conduct current preferentially in the inward direction. This inward rectification has two components: voltage-dependent blockade by intracellular Mg2+ (Mg2+i) and intrinsic gating. Two members of this channel family, IRK1 (ref. 10) and ROMK1 (ref. 11), differ markedly in affinity for Mg2+i (ref. 12). We found that IRK1 and ROMK1 differ in voltage-dependent gating and searched for the gating structure by large-scale and site-directed mutagenesis. We found that a single amino-acid change within the putative transmembrane domain M2, aspartate (D) in IRK1 to the corresponding asparagine (N) in ROMK1, controls the gating phenotype. Mutation D172N in IRK1 produced ROMK1-like gating whereas the reverse mutation in ROMK1--N171D--produced IRK1-like gating. Thus, a single negatively charged residue seems to be a crucial determinant of gating.

Amino Acid Sequence↗
PubMed1994

Strategies for the development of drugs for pharmacoresistant epilepsies.

Presently, most strategies for development of antiepileptic drugs (AEDs) center around seizure models that are known to respond to presently marketed AEDs. These strategies do not take into account that epilepsy can be a progressive disease. Moreover, region-specific aspects of epileptogenesis are rarely considered when new AEDs are developed. Seizures in the temporal lobe are often difficult to treat. Animal studies on various seizure models in the hippocampus and the entorhinal cortex (EC) suggest that these structures do not a priori produce seizures that are difficult to treat. However, seizure-like events in the EC tend to progress to a state of status epilepticus-like activity that cannot be suppressed by presently marketed AEDs. Loss of gamma-aminobutyric acid (GABA)ergic neurotransmission and increased excitatory synaptic coupling seem to cooperate for induction of this state. Epilepsy induced alterations in the interaction between the EC and the hippocampus may lead to alterations that facilitate precipitation of seizures. Because of the recurrent interaction between the hippocampus and the EC, these seizures may reach an intensity that is no longer controllable by presently available AEDs. Ontogenetic alterations of the circuitry between the EC and the hippocampus, seizure-induced stabilization of synaptic connections overexpressed during ontogenesis, seizure-induced lesions and subsequent rearrangements of internal cell properties, and synaptic arrangements and kindling-like alterations of nerve cell and glial behavior may all be involved in the generation of a neuronal aggregate whose balance between inhibitory and excitatory processes becomes readily disturbed. Strategies for the development of AEDs treating such seizures should suppress hyperactivity and prevent progression of epileptogenesis. AEDs directed against seizures may be effective if they can be given in sufficient concentrations to suppress very intense local seizures.

Animals↗
PubMed1992

Young CA1 pyramidal cells of rats, but not dentate gyrus granule cells, express a delayed inward rectifying current with properties of IQ.

In hippocampal CA1 pyramidal cells (CA1PC) and dentate gyrus granule cells (DGGC) we compared the expression of currents which could cause differences in discharge behaviour. Negative current injections cause a uniform hyperpolarization in DGGC whereas in CA1PC the initial hyperpolarization is followed by a repolarization towards resting membrane potential. The underlying inward current can be classified as IQ. It is sensitive to CsCl, activated at -80 mV, and it has a mean amplitude of -109.8 pA and a mean activation time constant of 187 ms with voltage jumps from -40 to -120 mV. We conclude that some of the differences in response properties of DGGC and CA1PC upon repetitive stimulation can be attributed to differences in the expression of IQ.

Animals↗
PubMed1992

Slow and fast transient potassium currents in cultured rat hippocampal cells.

1. Potassium currents have been recorded from rat hippocampal neurons in dissociated cultures prepared at E17-E19. Currents were studied with the whole-cell version of the patch clamp method. The kinetics and pharmacological properties of two transient outward currents have been characterized. 2. Most of the recordings have been done in cells which had been in culture 10-18 days. Both a fast and a slow transient current could be elicited. A subtraction procedure was used to isolate the fast transient current. The fast transient current decayed monoexponentially with a time constant of about 10 ms. The slow transient current decayed with two time constants in the order of 500 ms and of 3.4 s. The reversal potential of the slow current shifted by 54 mV for a tenfold change in extracellular potassium concentration. 3. Studies on the removal of inactivation for the two currents revealed time constants of 29 and 107 ms for the fast and slow transient current, respectively. 4. The steady-state inactivation properties of the fast transient current were determined by studying the current with a fixed depolarizing command of -10 mV and varying pre-pulse amplitudes from a holding potential of -50 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation occurred at -81 mV. The steady-state activation properties of the fast transient current were determined by varying the depolarizing voltage commands following a fixed pre-pulse to -110 mV. The threshold for activation was between -70 and -60 mV. Half-maximal activation was reached at -19 mV. 5. The steady-state inactivation properties of the slow transient current were determined by studying the current elicited by varying the hyperpolarizing voltage steps from a holding potential of 0 mV. The inactivation curve could be fitted with a Boltzmann equation. Half-maximal inactivation was obtained at -61 mV. The steady-state activation properties were determined in a manner similar to the fast current. The threshold for activation was between -40 and -30 mV. 6. The slow transient current was not inactivated immediately when the conditioning pre-pulse was stopped. The rate of current decay increased with stimulus frequency. 7. Both transient currents were sensitive to 4-aminopyridine (4-AP). The fast transient current was blocked completely by 5 mM provided a pre-pulse of 1 s to -110 mV was employed. The slow transient current was already depressed by 4-AP applied in the 100 microM range but could never be blocked completely.(ABSTRACT TRUNCATED AT 400 WORDS)

Action Potentials↗
PubMed1992

Properties of two voltage-activated potassium currents in acutely isolated juvenile rat dentate gyrus granule cells.

1. The properties of outward currents were investigated in acutely isolated dentate gyrus granule cells at postnatal ages of day 5-7, 10-14, 18-24 (P5-7, P10-14, P18-24) and at adulthood (2-3 mo), with the use of the whole-cell patch-clamp technique. 2. Kinetic analysis and pharmacological properties showed that an A-type K+ current (IA) and a delayed rectifier current (IK) were present in these cells. 3. IA in P10-14 cells activated and inactivated rapidly with a decay time constant of 7.5 +/- 2.1 (SD) ms with command pulses to +30 mV. The removal of inactivation was monoexponential with a time constant of 23.1 ms (holding potential, -50 mV; conditioning voltage steps of varying duration to -110 mV). V 1/2 of the Boltzmann function describing steady-state inactivation was -65.1 +/- 1.8 mV with a slope factor of -6.0. IA was sensitive to 5 mM 4-aminopyridine (4-AP) but not to 10 mM tetraethylammonium (TEA). 4. IK in P10-14 cells displayed a voltage-dependent activation time constant (4.3 +/- 0.8 ms for command pulses to +30 mV and 16.2 +/- 2.4 for command pulses to -10 mV) and a double-exponential decay (time constants 194 +/- 21 and 1,625 +/- 254 ms). The rate constant of removal of inactivation was 332.1 ms. IK showed a reduction by 61.4 +/- 5.3% with 10 mM TEA and was partially blocked by 5 mM 4-AP in a subpopulation of cells. 5. Whereas IA remained stable over time, IK showed a substantial reduction of current amplitude by 67% after 30 min of cell perfusion through the patch pipette. The time course of this reduction was monoexponential with a time constant of 6.9 min and was partly due to a shift in V1/2 of the steady-state inactivation from -79.2 to -99.6 mV. 6. IA and IK remained stable with respect to kinetic properties during ontogenesis. However, the relative contribution and pharmacological properties of the investigated K+ currents varied with age. Although IA dominated in P5-7 cells, IK was prominent in most older cells. Five millimolars 4-AP reduced IA by 40.7 +/- 26.7% in P5-7 cells and blocked IA completely in 80% of investigated P10-14 cells. Similar changes were observed for the effects of 4-AP on IK (18.7% depression in the age group P5-8, 46.1% in the age group P10-14, and 45.7% in adult animals).

4-Aminopyridine↗
PubMed1992

The dentate gyrus as a regulated gate for the propagation of epileptiform activity.

Properties of the interaction between the entorhinal cortex (EC) and the dentate gyrus were studied in a combined EC hippocampal slice preparation in which most of the fiber connectivity within this structure is intact. Epileptiform activity was induced by lowering extracellular Mg2+ concentration. This caused short recurrent discharges in the hippocampus while seizure-like events (SLE) slowly spread from the site of initiation to neighboring areas. At the end of a SLE, the EC, the subiculum and the neocortical area Te2 discharged in synchrony. This activity could develop into a state of recurrent tonic discharges highly synchronized between the different areas. These discharges were insensitive to treatment with currently available antiepileptic drugs. Although the SLE increased neuronal firing and extracellular potassium concentration in the dentate gyrus, this activity had only moderate effects on the activity generated in areas CA3 and CA1. Removing GABAergic inhibition with baclofen and bicuculline caused the spread of SLE from the EC to the dentate gyrus. Slow inhibitory postsynaptic potentials and intrinsic properties of dentate gyrus granule cells appear to underlie the filtering function of the dentate gyrus.

Afferent Pathways↗
PubMed1990

The accuracy of osteosynthesis repositioning of the mandible--a stereophotogrammetric study.

The accuracy of repositioning of wire and plate osteosyntheses is measured by means of close-up stereophotogrammetry on cadaver mandibles. An increase of the intercondylar distance, which increases by an average of about 3.3 mm after plate osteosynthesis and by about 1.9 mm after a wire suture, is characteristic for both methods of osteosynthesis. In addition, there is a tendency to displacement of the articular condyle to caudal in osteosyntheses at the base of the mandible.

Bone Plates↗
PubMed1984

[Calibration of pressure-measuring foil in biomechanics].

Concerning the calibration of the Prescale foil - a pressure sensitive foil, which shows a monochromatic, pressure depending coloration when loaded - some interesting new facts were ascertained. The coloration of the foil does not depend on the pressure load only, but also on the material of the pressing bodies. Calibration using hard material (high Elastic-Module, e.g. steel) results in a lower maximal optical density compared to soft material (low Elastic-Module, e.g. a hydraulic system) at the same pressure level. Due to wellknown facts of the pressure conditioned in a joint, a hydraulic system is more equivalent to joint conditions. Therefore, a calibration method based on a hydraulic system should be preferred if the Prescale foil is used in biomechanics. Furthermore, the density of coloration depends on the speed of pressure increase, too. A faster load of a particular pressure results in a denser coloration. Pressure increase during calibration shall be the same as during investigation. Both effects are statistically significant.

Ankle Joint↗
PubMed1981

[A new method for the determination of the weight-dependent course of pressure and contact in the articular surface].

A new method for measurements of pressure distributions and contact areas in joints. An innovative method is presented, allowing, for the first time, the exact determination of load-dependent pressure distributions and contact areas of joint surfaces in anatomical specimens. A thin flexible foil is inserted into the joint and adjust itself to curvatures. Upon loading, a monochromatic coloration occurs such that the optical density increases linearly with pressure. Using an electronic picture processor an analog representation of isobaric areas is obtained and evaluated, thereby integrating the areas of equal optical density. This procedure is considered to be superior to densitometric digital signal processing. For illustration, measurements of tibiofemoral-, patellafemoral- and ankle joints are shown, demonstrating the advantages and limitations of the new method.

Adult↗
PubMedDate not supplied

[Accuracy of apposition achieved by mandibular osteosyntheses. Stereophotogrammetric study].

The accuracy of apposition achieved by wire and plate osteosyntheses is measured with the aid of close range stereophotogrammetry in the mandibles of dead bodies. Both osteosynthesis methods are characterized by an increase in the intercondylar distance which, on the average, is about 3.3 mm greater after plate osteosynthesis and about 1.9 mm after wiring. Moreover, osteosyntheses of the base of the mandible may involve a tendency of the condyle to become caudally dislocated.

Bone Plates↗