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P Arhem

Publications and source records attributed to P Arhem.

At least 37 records · Page 2Linked to original sources
PubMed1994

Effects of gadolinium on ion channels in the myelinated axon of Xenopus laevis: four sites of action.

The action of gadolinium (Gd3+) on ion currents in myelinated axons of Xenopus laevis was investigated with the voltage clamp technique. The analysis revealed the following effects. (i) The potential-dependent parameters of both Na and K channels were shifted. The shift was equally large for activation, inactivation, and activation time constant curves (+9 mV for 100 microM Gd3+). The effects could be explained by screening of fixed surface charges at a density of -1.2 e nm-2. (ii) The rate of gating for both Na and K channels was reduced more than predicted from the shift. This effect could be quantified as a scaling (by a factor 3 and 5 respectively at 100 microM Gd3+) of the activation time constant curves. (iii) An activation- and inactivation-independent block of both Na and K channels, obeying 1:1 stoichiometry with a Kd value of about 70 microM potential-independent block of leakage current, obeying 1:2 stoichiometry with a Kd value of 600 microM. (iv) The analysis suggests separate binding sites for the effects, comprising high affinity modulatory and blocking sites on the channel proteins and low affinity receptors on phospholipids, associated with the effect on the leakage current.

Animals↗
PubMed1994

The modulatory site for the action of gadolinium on surface charges and channel gating.

The gadolinium (Gd3+)-induced shift of potential dependence and modulated gating of Na and K channels were analyzed. In a previous investigation, we explained the shift in terms of pure screening (no binding) of fixed surface charges and the modulation by binding to modulatory sites on the channels. In the present paper, we have extended this model by including effects on the charge density of Gd3+ binding to the modulatory sites. From fitting the extended model to experimental data, the charge density was estimated to be -0.6 e nm-2, and the Gd(3+)-induced charge change to be +0.15 e nm-2, and the maximal scaling factor to be 7.5 for both Na and K channels. Intrinsic KD values for binding to the K and Na channels were estimated to be 140 and 380 mM, respectively. Estimations of the extracellular charge density, from primary structures of cloned channels, were found to be in agreement with estimations based on the present model. The modulatory site was suggested to be located at the cluster of negatively charged residues between the fifth transmembrane segment (S5) and the pore-forming region for both Na and K channels. These suggestions imply several testable predictions about different K channels.

Animals↗
PubMed1993

A discussion of the mind-brain problem.

In this paper Popper formulates and discusses a new aspect of the theory of mind. This theory is partly based on his earlier developed interactionistic theory. It takes as its point of departure the observation that mind and physical forces have several properties in common, at least the following six: both are (i) located, (ii) unextended, (iii) incorporeal, (iv) capable of acting on bodies, (v) dependent upon body, (vi) capable of being influenced by bodies. Other properties such as intensity and extension in time may be added. It is argued that a fuller understanding of the nature of forces is essential for the analysis of the mind-brain problem. The relative autonomy and indeterministic nature of mind is stressed. Indeterminism is treated in relation to a theorem of Hadamard. The computer theory of mind and the Turing test are criticized. Finally the evolution of mind is discussed.

Biophysical Phenomena↗
PubMed1992

High concentrations of the neuroleptic remoxipride block voltage-activated Na+ channels in central and peripheral nerve membranes.

The actions of the neuroleptic compounds remoxipride, haloperidol and (-)-sulpiride on Na+ and K+ ion current flow were examined in rat CNS and frog PNS, using 86Rb+ ion flux and voltage-clamp techniques, respectively. By combining veratridine and high K(+)-evoked 86Rb+ efflux, it was determined that remoxipride blocked Na+ current flow in a concentration-dependent fashion in tissue pieces from either cerebral cortex or striatum (IC50 approximately 20 microM), leaving K+ current flow virtually unaffected. Similarly, haloperidol concentration dependently blocked Na+ current flow in both tissues (IC50 approximately 50 microM). (-)-Sulpiride did not have a significant effect. Direct actions of the compounds on voltage-gated Na+ and K+ channels were determined in voltage-clamp experiments. The findings confirmed the results of the ion flux measurements in that remoxipride (Kd approximately 300 microM) and haloperidol (Kd approximately 1.5 microM) reduced mainly the Na+ current, having little effect on the K+ current, whereas (-)-sulpiride did not have a measurable action. The relatively high concentrations of remoxipride or haloperidol needed to alter the Na+ current makes it unlikely that these actions are of importance at clinically relevant doses.

Animals↗
PubMed1992

Single K(+)-channel currents under steady-state potential conditions in small hippocampal neurons.

Small cultured hippocampal neurons from rat embryos were studied with the patch-clamp technique. Single-channel currents from outside-out membrane patches were recorded under steady-state potential conditions. The most frequently found channel types were selective to K+ and showed conductances of about 30 and 80 pS in the range -20 to 0 mV. Two basic kinetic patterns were observed for the 80 pS channels. In one type, the fraction of time spent in open state increased with potential, and in the other type it decreased. For both types of 80 pS channel, the distribution of dwell times in the open state was well described by the sum of two exponentials while three exponentials sometimes were required for dwell times in the closed state. The time constants of the fitted exponentials could vary considerably during an experiment.

Animals↗
PubMed1992

Mechanisms of propofol action on ion currents in the myelinated axon of Xenopus laevis.

The effect of the intravenous anaesthetic, propofol (2,6-diisopropylphenol), was investigated on frog myelinated axons under voltage-clamp conditions. The effect, in the concentration range 60 microM to 10 mM, was a combination of (i) a negative shift of the steady state activation and inactivation curves for both Na+ and K+ currents (INa,IK), (ii) a voltage-independent block of INa, but not of IK, and (iii) a slowed time course of IK activation. The shift was dose-dependent and, at 1 mM, about -10 mV for the activation and -16 mV for the inactivation curves. The voltage-independent INa block showed 1:1 stoichiometry and 50% reduction at 2.7 mM. The slowed IK activation showed saturation at 1 mM with a doubled time to half steady state value. All the effects were only partially reversible and showed a complex time course at application and washing. The shift of potential dependence may be explained by a general effect on the membrane electric field. The findings suggest effects directly on channel proteins as well as on membrane lipids.

Anesthetics↗
PubMed1992

Impulses of variable amplitude recorded from cell-attached patches on small hippocampal neurons.

Small cultured neurons from embryonic rat hippocampus were investigated with the cell-attached configuration of the patch-clamp technique. The currents associated with spontaneous cellular impulse generation were studied. The positive peak current amplitudes varied by a factor larger than 2.5 for 11 of 12 cells quantitatively investigated, suggesting underlying action potentials of variable amplitude. A simple RC-network was found to describe the properties of the patch membrane, and was used to calculate the underlying potential time course. The action potentials computed showed a considerable variation in amplitude. The results suggest that the impulse variability previously analysed with the whole-cell technique was not caused by dialysis of the cell interior.

Action Potentials↗
PubMed1992

Impulses and resting membrane properties of small cultured rat hippocampal neurons.

1. The impulses and resting membrane parameters of small (soma diameter less than 10 microM) cultured hippocampal neurons from rat embryos were studied with the tight-seal whole-cell recording technique. 2. Mean resting potential was -47 mV, mean input resistance 3.3 G omega, mean capacitance 11 pF, and mean time constant 33 ms. 3. Rectangular suprathreshold current steps elicited regenerative potential responses. The amplitude and time course of the responses were clearly stimulus dependent: stronger current steps caused impulses of larger amplitude. 4. The current threshold was very low: rheobase current was less than 15 pA. 5. The potential response depended on the preceding holding potential, responses from more negative potentials showing sharper peaks than those from more positive potentials. 6. Spontaneous impulses with pre-potentials similar to synaptically induced events were recorded from several cells. The amplitude of the spontaneous impulses varied similarly to that of the stimulus-induced responses.

Action Potentials↗
PubMed1992

Membrane currents in small cultured rat hippocampal neurons: a voltage-clamp study.

1. The currents underlying the graded impulses in small cultured hippocampal neurons from rat embryos were analysed under voltage-clamp conditions with the tight-seal whole-cell recording technique. 2. The leak and capacitative currents induced by a potential step were linearly related to the potential in the range studied (-60 to -100 mV). 3. With steps to potentials more positive than -40 mV, at least two different potential-activated currents were detected: an initial transient current and a delayed sustained one. In addition, 40% of the cells studied showed a delayed transient current. 4. The initial transient current showed sigmoid activation and roughly exponential inactivation. Its reversal potential depended on the Na+ concentration and was close to the Na+ equilibrium potential. Further, it was blocked by 3.0 microM-tetrodotoxin, and was abolished when choline was substituted for Na+ in the extracellular solution. We concluded that this current was carried mainly by Na+ ions. 5. The delayed sustained current showed sigmoid activation and almost no inactivation within 40 ms. The reversal potential was close to the K+ equilibrium potential. We concluded that this current was carried mainly by K+ ions. 6. The delayed transient current was outward in the potential range studied (-50 to +120 mV) and did not depend on the pipette Cl- concentration. It was assumed that this current was carried mainly by K+ ions. 7. A quantitative description of the initial transient and the delayed sustained currents was developed on the basis of earlier descriptions of excitable membranes.

Animals↗
PubMed1992

Computed potential responses of small cultured rat hippocampal neurons.

1. The potential responses of small hippocampal neurons were computed on the basis of a previous mathematical description of the currents recorded under voltage-clamp conditions. 2. The computed action potentials were graded with respect to stimulus strength, in accordance with previous experimental findings. 3. The time course of the membrane currents and of the permeabilities and permeability variables during the impulse was computed for different stimulus intensities. 4. The effect of the membrane time constant on the impulse amplitude was investigated. It was concluded that the value of the time constant used was not per se sufficient to explain the amplitude variation of the impulse. 5. The effect of the magnitudes of the different potential-dependent permeabilities on the impulse amplitude was investigated. A Na+ permeability within a certain range caused impulses of variable amplitude, and this variability was affected by the K+ permeability.

Action Potentials↗
PubMed1991

Mechanisms of the tetrahydroaminoacridine effect on action potential and ion currents in myelinated axons.

9-Amino-1,2,3,4-tetrahydroacridine (THA) in the range of 10-300 microM was shown to prolong the action potential in myelinated nerve fibres of Xenopus laevis. Voltage-clamp experiments showed that THA, besides reducing the Na+ and the K+ current, modified the Na+ current inactivation and the K+ current activation. The effects were frequency dependent. Quantitative models were developed and used in computer simulations of the THA effect on the action potential. The computations showed that the observed effects on the ion currents were sufficient to explain the observed prolongation of the action potential. The models further suggest that THA binds to Na+ channels in an open state and from the axoplasmic side while it binds to K+ channels in a closed state. The findings suggest an explanation to some aspects of the clinical effects of THA on Alzheimer patients.

Action Potentials↗
PubMed1991

Properties of the leakage current pathway: effects of the gadolinium ion on myelinated axons.

Voltage-clamp experiments on myelinated axons revealed that the trivalent gadoliniumion ion blocked the leakage current in a dose-dependent manner. The block showed 1:2 stoichiometry, and 50% reduction at 700 microM. Na+ and K+ currents were blocked at ten times lower concentration and showed 1:1 stoichiometry. Comparisons with biochemical studies suggest that the leakage current directly depends on a phospholipid pathway in contrast to the protein-channel dependent Na+ and K+ currents. The results may be explained by a leakage current pathway located at the interface between channel proteins and the lipid phase.

Animals↗
PubMed1990

Single-channel and whole-cell currents in rat cerebellar granule cells.

The patch-clamp technique was used to study both whole-cell and single-channel currents in cultured rat cerebellar granule cells. In whole-cell recordings under voltage-clamp conditions 3 types of current were found; a transient inward sodium current and a transient and a sustained outward potassium current. Single-channel currents were recorded from both inside-out and outside-out membrane patches. Three types of potassium channel were identified; two non-inactivating channels with unit conductances of 160 and 60 pS and one inactivating channel of 20 pS. No calcium currents were detected.

Action Potentials↗
PubMed1990

Graded action potentials in small cultured rat hippocampal neurons.

The 'all-or-nothing' principle has been central to neurobiology since the beginning of this century. We here demonstrate that action potentials in small cultured neurons from the hippocampus of rat embryos clearly depend on stimulus strength and thus deviate from this principle. We also demonstrate that similar stimulus-dependent action potentials can be predicted from computations based on voltage-clamp measurements. The findings suggest that amplitude modulation of the action potential may be a principle for information processing in the mammalian nervous system.

Action Potentials↗
PubMed1989

Effects of THA on ionic currents in myelinated axons of Xenopus laevis.

In voltage-clamp experiments with the myelinated nerve fibre of Xenopus laevis, 9-amino-1,2,3,4-tetrahydroacridine (THA) decreased both Na+ and K+ currents and shifted the steady state inactivation potential curve in a negative direction. The effects may be described as (a) a decrease of the permeability constant PNa, (b) a modified potential dependence of the inactivating system and (c) a decrease of PK. The Na+ system was affected more than the K+ system.

Aminoacridines↗
PubMed1989

Action potentials of cultured human oat cells: whole-cell measurements with the patch-clamp technique.

Oat cells (of the small cell carcinoma of the lung) have been reported to generate calcium action potentials. The calcium channels have further been suggested to play a crucial role in the relation between oat cell carcinoma and the often associated myasthenic syndrome. We have examined cultured human oat cells (U-1690) under voltage-clamp conditions, using the patch-clamp technique. We found, contrary to previous reports, that the action potential was caused by sodium and potassium currents. No calcium current was detected under these conditions, which indicates that calcium channels, if present, are very rare. The findings restrict, but do not rule out, the hypothesis that calcium plays a key role in the carcinoma/myasthenic syndrome relation.

Action Potentials↗