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P Grafe

Publications and source records attributed to P Grafe.

At least 73 records · Page 4Linked to original sources
PubMed1985

Activity-dependent excitability changes in normal and demyelinated rat spinal root axons.

Myelinated nerve fibres with a reduced safety factor for conduction due to demyelination are easily blocked by trains of impulses. To find out why, in vivo recordings from rat ventral root fibres demyelinated with diphtheria toxin have been supplemented with in vivo and in vitro recordings from normal fibres. Despite a small rise in extracellular potassium activity, normal fibres were invariably hyperpolarized by intermittent trains of impulses. This hyperpolarization resulted in an increase in threshold and also in an enhancement of the depolarizing after-potential and the superexcitable period. Replacement of NaCl in the extracellular solution by LiCl completely blocked both the membrane hyperpolarization and the threshold increase which were normally observed during intermittent trains of impulses. At demyelinated nodes which were blocked by trains of impulses (10-50 Hz), conduction block was preceded by a rise in threshold current and in an increase in internodal conduction time, but by no detectable reduction in the outward current generated by the preceding node. It was found possible to prevent the threshold from changing during a train by automatic adjustment of a d.c. polarizing current. This 'threshold clamp' prevented the conduction failure and virtually abolished the changes in internodal conduction time. The threshold changes were attributed to hyperpolarization, as in normal fibres, since (a) the polarizing current required to prevent them was always a depolarizing current, and (b) they were accompanied by an increase in superexcitability. The post-tetanic depression that can follow continuous trains of impulses was attributed to the combination of increased threshold and enhanced superexcitable period due to hyperpolarization. It is concluded that the susceptibility of these demyelinated fibres to impulse trains is not due to a membrane depolarization induced by extracellular potassium accumulation but to a membrane hyperpolarization as a consequence of electrogenic sodium pumping.

Action Potentials↗
PubMed1984

Different types of potassium transport linked to carbachol and gamma-aminobutyric acid actions in rat sympathetic neurons.

Carbachol and gamma-aminobutyric acid depolarize mammalian sympathetic neurons and increase the free extracellular K+-concentration. We have used double-barrelled ion-sensitive microelectrodes to determine changes of the membrane potential and of the free intracellular Na+-, K+- and Cl- -concentrations ( [Na+]i, [K+]i and [Cl-]i) during neurotransmitter application. Experiments were performed on isolated, desheathed superior cervical ganglia of the rat, maintained in Krebs solution at 30 degrees C. Application of carbachol resulted in a membrane depolarization accompanied by an increase of [Na+]i, a decrease of [K+]i and no change in [Cl-]i. Application of gamma-aminobutyric acid also induced a membrane depolarization which, however, was accompanied by a decrease of [K+]i and [Cl-]i, whereas [Na+]i remained constant. Blockade of the Na+/K+-pump by ouabain completely inhibited both the reuptake of K+ and the extrusion of Na+ after the action of carbachol, and also the post-carbachol undershoot of the free extracellular K+-concentration. On the other hand, in the presence of ouabain, no changes in the kinetics of the reuptake of K+ released during the action of gamma-aminobutyric acid could be observed. Furosemide, a blocker of K+/Cl- -cotransport, inhibited the reuptake of Cl- and K+ after the action of gamma-aminobutyric acid. In summary, the data reveal that rat sympathetic neurons possess, in addition to the Na+/K+-pump, another transport system to regulate free intracellular K+-concentration. This system is possibly a K+/Cl- -cotransport.

Animals↗
PubMed1984

Phasic variations of extracellular potassium during fictive swimming in the lamprey spinal cord in vitro.

The lamprey spinal cord in vitro can generate the motor pattern underlying locomotion, which can be recorded with suction electrodes in the ventral roots. To test if the extracellular level of potassium changed during rhythmic activity, potassium-sensitive microelectrodes were used to systematically (every 25 micrometers) explore the level of extracellular potassium [K+]e in different loci in the transverse plane of the spinal cord. During fictive locomotion the baseline level of [K+] increased with 0.08-0.4 mM in the grey matter. As a rule phasic variations of up to 0.2 mM, correlated to each ventral root burst, were superimposed on the tonic deviation of [K+]e. Changes in this range may cause a moderate depolarization of the spinal neurones and might also affect other neuronal functions including the rhythm-generating circuits.

Animals↗
PubMed1983

Effects of lithium on electrical activity and potassium ion distribution in the vertebrate central nervous system.

Three different regions of the vertebrate central nervous system maintained in vitro (frog spinal cord, guinea pig olfactory cortex and hippocampus) have been used to investigate how Li+ influences membrane potential, membrane resistance, action potentials, synaptic potentials and the transmembrane K+-distribution of neurons and glial cells. In view of the therapeutic action of Li+ in manic-depressive disease, a special effort was made to determine the threshold concentration for the actions of Li+ on the parameters described above. It was observed that Li+ induced a membrane depolarization of both neurons and glial cells, a decrease of action potential amplitudes, a facilitation of monosynaptic excitatory postsynaptic potentials and a depression of polysynaptic reflexes. The membrane resistance of neurons was not altered. Li+ also induced an elevation of the free extracellular potassium concentration and a decrease of the free intracellular potassium concentration. Furthermore, in the presence of Li+ a slowing of the recovery of the membrane potential of neurons and glial cells, and of the extracellular potassium concentration after repetitive synaptic stimulation was observed. The threshold concentrations for the effects of Li+ were below 5 mmol/l in the frog spinal cord and below 2 mmol/l in the guinea pig olfactory cortex and hippocampus. The basic mechanism underlying the action of Li+ may be an interaction with the transport-function of the Na+/K+ pump.

Animals↗
PubMed1983

Intracellular free sodium and potassium, post-carbachol hyperpolarization, and extracellular potassium-undershoot in rat sympathetic neurones.

Double-barrelled ion-sensitive microelectrodes were used to record the free intracellular Na+- and K+-concentrations [( Na+]i, [K+]i) and to determine their relation to changes in membrane potential and extracellular K+ [( K+]e) in rat sympathetic ganglia. The application of 50 mumol/l carbachol resulted in an elevation of [K+]e followed by a post-carbachol [K+]e-undershoot. The membrane depolarization of the sympathetic neurones was associated with an increase in [Na+]i and a decrease in [K+]i. A membrane hyperpolarization and a recovery of [K+]i and [Na+]i to their baseline levels were observed during the [K+]e-undershoot. The time course of the [K+]e-undershoot correlated exactly with the duration of the rise in [Na+]i and decrease of [K+]i. No K+-reuptake occurred in the presence of ouabain. These data confirm, by direct measurements of intracellular ion concentration changes, the contribution of the Na+,K+-pump to the post-carbachol membrane hyperpolarization and [K+]e-undershoot.

Animals↗
PubMed1982

Convulsant actions of 4-aminopyridine on the guinea-pig olfactory cortex slice.

The effects of bath-applied 4-aminopyridine on neurones and extracellular potassium and calcium concentrations were recorded in slices of guinea-pig olfactory cortex. Neurones were orthodromically activated by stimulating the lateral olfactory tract. 4-Aminopyridine (3-10 microM) had the following effects: (1) an increase in the frequency and amplitude of spontaneous postsynaptic potentials; (2) a prolongation and oscillatory behaviour of orthodromically evoked postsynaptic potentials; (3) induction of spontaneous or stimulus-evoked seizure-type discharges which were accompanied by large rises in extracellular potassium and falls in calcium concentration; (4) a prolongation of the lateral olfactory tract population fibre spike. Prior to paroxysmal depolarization, membrane potential, input resistance and soma spike duration were unaffected. In the seconds before seizure discharges, a late hyperpolarizing potential (evoked by orthodromic stimulation) was reduced in amplitude or abolished. Diphenylhydantoin (50 microM) or magnesium ions (5 mM) prevented paroxysmal activity. Our results show that 4-aminopyridine can produce seizure-type discharges in a brain slice preparation. The role of increased spontaneous potentials and possible loss of synaptic inhibition as causal factors for such discharges is discussed.

4-Aminopyridine↗
PubMed1982

Lithium distribution across the membrane of motoneurons in the isolated frog spinal cord.

Lithium sensitive microelectrodes were used to investigate the transmembrane distribution of lithium ions (Li+) in motoneurons of the isolated frog spinal cord. After addition of 5 mmol.1(-1) LiCl to the bathing solution the extracellular diffusion of Li+ was measured. At a depth of 500 micrometers, about 60 min elapsed before the extracellular Li+ concentration approached that of the bathing solution. Intracellular measurements revealed that Li+ started to enter the cells soon after reaching the motoneuron pool and after up to 120 min superfusion, an intra - to extracellular concentration ratio of about 0.7 was obtained. The resting membrane potential and height of antidromically evoked action potentials were not altered by 5 mmol.1(-1) Li+.

Animals↗
PubMed1982

Changes of intracellular sodium and potassium ion concentrations in frog spinal motoneurons induced by repetitive synaptic stimulation.

A post-tetanic membrane hyperpolarization following repetitive neuronal activity is a commonly observed phenomenon in the isolated frog spinal cord as well as in neurons of other nervous tissues. We have now used double-barrelled Na+- and K+-ion-sensitive microelectrodes to measure the intracellular Na+- and K+-concentrations and also the extracellular K+-concentration of lumbar spinal motoneurons during and after repetitive stimulation of a dorsal root. The results show that the post-tetanic membrane hyperpolarization occurred at a time when the intracellular [Na+] reached its maximal value, intracellular [K+] had its lowest level and extracellular [K+] was still elevated. The hyperpolarization was blocked by ouabain and reduced by Li+. These data support the previous suggestion that an electrogenic Na+/K+ pump mode may be the mechanism underlying the post-tetanic membrane hyperpolarization.

Animals↗
PubMed1980

Presynaptic actions of 4-aminopyridine and gamma-aminobutyric acid on rat sympathetic ganglia in vitro.

Responses to bath-applications of 4-aminopyridine(4-AP) and gamma-aminobutyric acid (GABA) were recorded intracellularly from neurones in the rat isolated superior cervical ganglion. 4-aminopyridine (0.1-1.0 mmol/l) usually induced spontaneous action potentials and excitatory postsynaptic potentials (EPSPs), which were blocked by hexamethonium. Membrane potential was unchanged; spike duration was slightly increased. Vagus nerve B- and C-fibre potentials were prolonged. In 4-AP solution (0.2-0.3 mmol/l), GABA (0.1 mmol/l), 3-aminopropanesulphonic acid or muscimol evoked "bursts" of spikes and EPSPs in addition to a neuronal depolarization. These "bursts", which were not elicited by glycine, glutamate, taurine or (+/-)-baclofen, were completely antagonised by hexamethonium, tetrodotoxin or bicuculline methochloride. It is concluded that: (a) 4-AP has a potent presynaptic action on sympathetic ganglia; (b) presynaptic actions of GABA can be recorded postsynaptically in the presence of 4-AP; and (c) the presynaptic GABA-receptors revealed in this condition are similar to those on the postsynaptic membrane.

Action Potentials↗
PubMed1980

Synaptic modulation of calcium-dependent potassium conductance in myenteric neurones in the guinea-pig.

1. Ganglion cells of the myentric plexus of the guinea-pig small intestine were studied with intracellular recording methods. 2. Electrical stimulation of the interganglionic connectives elicited slow synaptic excitation (slow e.p.s.p.) that was associated with an increase in the input resistance of the cell. The slow e.p.s.p.s continued for several seconds after termination of stimulation, and they occurred only in neurones in which prolonged hyperpolarizing after-potentials followed an action potential. 3. Superfusion of the neurones with solutions containing either 1-5 mM-Mn2+ or 16 mM-Mg2+ and 1 mM-Ca2+ mimicked the slow e.p.s.p. The common characteristics of Mn2+, Mg2+ and the slow e.p.s.p. were: (a) depolarization of the membrane potential, (b) increased input resistance of the cell, (c) augmented excitability, (d) blockade of post-pike hyperpolarizing potentials and (e) reversal potential between -70 and -75 mV. 4. Analyses based on the 'constant field equation' indicated that the permeability ratios of K+ to other permeant ionic species were reduced when Ca2+ influx was blocked by Mn2+ or Mg2+. 5. The organic Ca antagonist D-600 did not affect the neurones. 6. The results suggest that slow synaptic modulation of excitability within the myenteric plexus involves a reduction of both resting GK and post-spike GK which is secondary to suppression of Ca2+ influx by the neurotransmitter for the slow e.p.s.p.

Animals↗
PubMed1977

Effects of guanidine on synaptic transmission in the spinal cord of the frog.

The effects of guanidine on motoneurons of the isolated frog spinal cord were studied by adding the drug to the solution bathing the cord during intracellular recording. Guanidine (5.10(-4) M) did not alter the membrane potential of motoneurons. The main effect was a marked increase of the amplitudes and frequencies of small spontaneously occurring inhibitory postsynaptic potentials. The hyperpolarizing component of postsynaptic potentials evoked by stimulation of dorsal roots was also enhanced by guanidine. Higher concentrations of guanidine (5.10(-3) M) resulted in a very large and irreversible increase of the small spontaneously occurring inhibitory potentials, which now appeared in a regular, rhythmic pattern. The effects of guanidine could easily be blocked by increasing the magnesium ions (15 mM) in the bath solution. These results indicate that guanidine facilitates the release of an inhibitory transmitter in afferent terminals of the frog spinal cord either by a direct action on these terminals or indirectly by an action on nerve endings impinging on inhibitory interneurons.

Action Potentials↗
PubMed1975

Inhibitory postsynaptic actions of taurine, GABA and other amino acids on motoneurons of the isolated frog spinal cord.

The actions of glycine, GABA, alpha-alanine, beta-alanine and taurine were studied by intracellular recordings from lumbar motoneurons of the isolated spinal cord of the frog. All amino acids tested produced a reduction in the amplitude of postsynaptic potentials, a blockade of the antidromic action potential and an increase of membrane conductance. Furthermore, membrane polarizations occurred, which were always in the same direction as the IPSP. All these effects indicate a postsynaptic inhibitory action of these amino acids. When the relative strength of different amino acids was compared, taurine had the strongest inhibitory potency, followed by beta-alanine, alpha-alanine, GABA and glycine. Topically applied strychnine and picrotoxin induced different changes of post-synaptic potentials, indicating that distinct inhibitory systems might be influenced by these two convulsants. Interactions with amino acids showed that picrotoxin seletively diminished the postsymaptic actions of GABA, while strychnine reduced the effects of taurine, glycine, alpha- and beta-alanine. But differences in the susceptibility of these amino acid actions to strychnine could be detected: the action of taurine was more sensitively blocked by strychnine compared with glycine, alpha- and beta-alanine. With regard to these results the importance of taurine and GABA as transmitters of postsynaptic inhibition on motoneurons in the spinal cord of the frog is discussed.

Alanine↗