Potassium channels in human glioma cells.
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Cell Line↗
Biomedical subjects
T Brismar
Publications and source records attributed to T Brismar.
Properties of appropriately and inappropriately expressed sodium channels in squid giant axon and its somata.
Neurons that form the giant axons in squid by axonal fusion in the stellate ganglion are inexcitable and do not express functional voltage-controlled sodium (Na) channels in their somata in vivo. These cells do express Na channels in the soma membrane in vitro, however, provided they have been axotomized. We describe here voltage-clamp experiments on the isolated cell bodies maintained in primary culture and on acutely isolated giant axons designed to compare the functional properties of the Na channels expressed inappropriately in the soma with those of channels expressed normally in the axon. Approximately 85% of Na channels in the soma are essentially indistinguishable from those in the giant axon with regard to gating properties and sensitivity to tetrodotoxin or saxitoxin. Thus, the isolated soma is capable of processing Na channels to a state of apparent functional perfection. In addition to these normal Na channels, another type is regularly expressed in the cultured somata. This second type lacks inactivation and is preferentially sensitive to block by cadmium ions, but is otherwise indistinguishable from the more prevalent normal type of channels.
Animals↗
Inward K-current in human malignant glioma cells: possible mechanism for K-homeostasis in the brain.
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Brain↗
Nodes of Ranvier in acrylamide neuropathy: voltage clamp and electron microscopic analysis of rat sciatic nerve fibres at proximal levels.
Adult male rats were injected with acrylamide monomer (50 mg/kg i.p., 3 times/week). The animals developed hind limb paresis and distal motor nerve conduction velocity decreased. Three of 14 examined isolated myelinated sciatic nerve fibres showed a reduced excitability. In the remaining fibres the action potentials were normal. Potential clamp analysis of nodes of Ranvier in the single fibres revealed large delayed nodal K currents in 6 cases. Four of these 6 fibres exhibited a markedly increased membrane capacitance and in 2 fibres an increased Na permeability was found. Electron microscopic examination of sciatic nerves revealed comparatively subtle internodal and nodal-paranodal alterations in large myelinated fibres. Internodally, focal aggregates of tubulovesicular profiles could be found and some Schwann cells were hypertrophic. Paranodally, axonal evaginations penetrated in between the terminating myelin lamellae. Some paranodes had a very thin myelin covering and/or exhibited varying degrees of myelin sheath retraction. In the nodal axon domains lacking an axolemmal undercoating and partly non-undercoated axolemmal protrusions could be found. Similar physiological and morphological alterations occur in the rat sciatic nerve above a neuroma. Therefore, the presently observed proximal changes may, to some extent, represent non-specific alterations, secondary to a target deprivation caused by the distal axon degeneration typical for acrylamide neuropathy.
Acrylamide↗
Voltage-clamp analysis of nodes of Ranvier in regenerated rat sciatic nerve.
Crush-lesioned adult rat sciatic nerves were allowed to regenerate during 70-181 days. Single large regenerated nerve fibres were isolated from levels distal to the crush site, and mounted in a feedback system for potential recordings and voltage clamp. After the experiment, each isolated fibre was fixed and embedded for morphological evaluation. Internodal lengths and fibre diameters were obtained form teased preparations of regenerated and normal sciatic nerves. The isolated regenerated fibres were excitable and had action potentials of large amplitude. TEA and 4-AP had negligible effects on the action potential and excitability properties. The time constant of the nodal segment was larger than in normal fibres. The nodal Na and K permeabilities (PNa and PK) were calculated both in absolute values and relative to the leak conductance (gL). Regenerated fibres had normal PNa/gL and PK/gL ratios. The potential dependence of PNa activation and inactivation was also normal. The isolated physiologically examined fibres had internodal lengths (L) of about 300 micron and diameters (D) of about 7-11 micron. In the teased fibre preparations L was about 300 micron (range 150-600 micron) and D was 3-11 micron. In addition, all teased regenerated nerve preparations exhibited a few scattered unusually short internodes (L less than 150 micron). In control nerves L ranged from 150 micron in the lower fibre size range (D = 2-3 micron) to 1.6 mm in the upper size range (D = 15 micron).
Action Potentials↗
Reversible and irreversible nodal dysfunction in diabetic neuropathy.
Acute reversible diabetic nerve dysfunction has been associated with a reversible myo-inositol-related (Na+ + K+)-ATPase defect, while poorly reversible chronic nerve dysfunction correlates with progressive axoglial dysjunction of peripheral nerve. The causal relationships between biochemical and neuroanatomical abnormalities and those of nodal membrane function are not known. Nodal clamp examinations were carried out in the sciatic nerve of diabetic BB-rats to elucidate the events underlying diabetic nerve dysfunctions and how these relate to metabolic and structural defects of diabetic nerve. With increasing duration of diabetes, there was a progressive decline in nodal action potentials attributable to decreased Na+ permeability and a decrease in the membranous Na+ gradient. Vigorous insulin therapy in short-term (6-week) diabetic BB-rats normalized the Na+-permeability defect and the membranous Na+ gradient. These defects did not reverse in long-term (24-week) diabetic animals subjected to the same treatment. This poorly reversible nodal dysfunction accounts for the not readily reversible conduction defect in chronic diabetes and is probably directly related to irreversible axoglial dysjunction.
Animals↗
T-lymphocyte subsets, functional deficits, and morphology in sciatic nerves during experimental allergic neuritis.
Conduction velocities, demyelination, "macrophage/dendritic" cells, different sets of T-lymphocytes, and immunoglobulins were estimated in sciatic nerves during various phases of experimental allergic neuritis in Lewis rats. Demyelination was minimal day 15 postimmunization (p.i.) when conduction velocity already was reduced, somewhat more pronounced day 17 p.i. when nerve conduction was blocked, and most pronounced day 23 p.i. when nerve conduction partially had recovered. This suggests a dissociation between the degree of demyelination and the functional deficits. Decrease of sciatic nerve conduction velocities coincided with endoneurial appearance of T-lymphocytes and "macrophage/dendritic" cells, as well as endoneurial immunoglobulins, day 15 p.i. Later partial functional recovery occurred in parallel with the disappearance of T-cells. The degree of functional deficits thus correlated with the number of endoneurial T-lymphocytes. T-cells may, directly or indirectly, initiate several of the disease components in experimental allergic neuritis, including the nerve conduction deficit.
Animals↗
Synthesis of sodium channels in the cell bodies of squid giant axons.
Giant axons in squid are formed by fusion of axons from many small cell bodies in the giant fiber lobe (GFL) of the stellate ganglion. Somata of GFL cells in vivo are inexcitable and do not have measurable sodium current (INa) when studied with microelectrode or patch-electrode voltage-clamp techniques. If GFL cells are separated from the giant axons and maintained in primary culture, axon-like INa can be recorded from the somata after several days. Incorporation of Na channels into GFL cell bodies requires protein synthesis, intracellular microtubule-based transport, and the lack of a morphologically defined axon to serve as a sink for channels synthesized in culture.
Animals↗
Nodes of Ranvier above a neuroma in the rat sciatic nerve: voltage clamp analysis and electron microscopy.
Neuroma formation was induced in adult rat sciatic nerves and the animals were allowed to survive for 1-10 months. In 10 animals single large myelinated fibres from the nerve segment above the neuroma were subjected to voltage clamp analysis. Six animals were fixed by glutaraldehyde perfusion and nodes of Ranvier or large myelinated fibres above the neuroma were examined in the electron microscope (EM). Most fibres exhibited normal action potentials, but a few had a reduced excitability and small action potentials. Some fibres had increased membrane time constant and leak conductance and a markedly increased membrane capacitance. Most of the examined nodes of Ranvier exhibited abnormally large delayed K currents, which could be blocked with 4-aminopyridine (4-AP). The Na current was normal. In the EM most large cross-cut myelinated axons were markedly atrophic, particularly after long survival times. Evaginations from the paranodal region of these axons penetrated between the terminating paranodal myelin lamellae. The nodal axolemmal undercoating could be very prominent and in some cases the nodal axon was irregular. These findings show that large myelinated peripheral nerve fibres, which are chronically disconnected from their peripheral targets, exhibit specific structural and functional abnormalities of the nodes of Ranvier.
Amputation Stumps↗
Reversible diabetic nerve dysfunction: structural correlates to electrophysiological abnormalities.
Structural alterations of the nodal and paranodal areas were examined in the posterior tibial nerve in insulin-depleted and insulin-treated diabetic BB rats. The early metabolic phase of the distal symmetrical polyneuropathy was characterized by paranodal axonal swellings and nodal bulgings of the axon. These alterations correlate with intraaxonal sodium accumulation and decreased sodium equilibrium potentials which account for the early nerve conduction defect. Both the structural and electrophysiological abnormalities were completely normalized after vigorous insulin therapy. In the chronic diabetic polyneuropathy the paranodal area showed loss of paranodal axoglial junctions and paranodal myelin retraction. These changes may be partially responsible for the impaired electrical activity at the node as exemplified by irreversibly impaired sodium permeability and nerve conduction.
Animals↗
Excitability changes reveal decreased sodium permeability in neuropathy.
Nerve excitability was tested in isolated sciatic nerves of rats with acute uremia. Larger than normal stimulating pulses were required to elicit a maximal compound potential, whereas the relative refractory period was unaffected. The threshold range, relative to the absolute threshold, was a good measure of the decreased excitability and may be a useful clinical method.
Animals↗
Changes in electrical threshold in human peripheral neuropathy.
A new method for analysis of excitability changes in human peripheral neuropathy is described. The range of the electrical threshold in a nerve is estimated in relative units from the ratio (S90-S10)/S10, where S10 and S90 are the stimulus voltages for 10% and 90% of maximal compound muscle potential. The ratio is increased if there is a fraction of high threshold fibres in the nerve; it is not affected by extraneural factors (e.g. distance to the nerve). The ratio was 0.16 +/- 0.03 in normals and significantly higher in subjects with chronic renal insufficiency or diabetes mellitus. Some of these had normal nerve conduction velocity. The ratio was markedly increased in the median nerve at the wrist in subjects with the carpal tunnel syndrome, which indicated that there are retrograde changes in the entrapped nerve fibres.
Adult↗
Nerve conduction in diabetic pregnancy. A prospective study.
Repeated neurographic examinations were performed during and after the pregnancies of 32 diabetic women who had no signs of neuropathy before pregnancy or at the initial examination during the first trimester. The motor conduction velocity, the sensory conduction velocity and the peak amplitude of the compound action potential of the investigated peripheral nerves were not affected by pregnancy. It is concluded that pregnancy does not impair nerve conduction or induce neuropathy in most diabetic women.
Action Potentials↗
Potassium permeability in rat myelinated nerve fibres.
Potential clamp experiments were performed at 21-23 degrees C on single myelinated rat nerve fibres isolated from the sciatic nerve. A small delayed K-permeability (PK) was regularly identified in the normal rat node amounting to 0.067 cm3 s-1 X 10(-9) at large positive potentials. Measurements in isotonic KCl showed that about two-thirds of PK was already activated at resting potential. Substitution of Cs for axoplasmic K demonstrated that the rat node had large leak currents (33 nS). The leak current provided the main part of the repolarizing outward current. 10 mM tetraethylammonium chloride (TEA) slowly (tau approximately equal to 2 min) and incompletely (50%) blocked both PK activated at resting potential and the delayed increase in PK. I mM 4-aminopyridine (4-AP) had less effect on PK.
Animals↗
Experimental uremic neuropathy. Part 1. Decreased nerve conduction velocity in rats.
Acute and chronic renal failure were induced in adult male albino rats by conventional surgical methods. The glomerular filtration rate of rats with chronic uremia was reduced to approximately 15% of normal. Despite this drastic degree of renal failure, the motor nerve conduction velocity (MCV) increased from 47.5 +/- 6.4 m/s, preoperatively, to 55.6 +/- 4.0 m/s after 4 weeks. In rats with acute uremia, MCV decreased from 51.4 +/- 3.0 m/s to 45.2 +/- 2.7 m/s after 48 h. The conduction velocity, measured in vitro of excised sciatic nerves was 55.2 +/- 4.4 m/s in acute uremia and 64.7 +/- 4.7 m/s in a control group. There was no difference in the refractory period between these groups. It is concluded that this decrease in the nerve conduction velocity was not caused by changes in the composition of the extracellular fluid but rather by changes in the nodal membrane function.
Acute Kidney Injury↗
Experimental uremic neuropathy. Part 2. Sodium permeability decrease and inactivation in potential clamped nerve fibers.
Potential recordings and potential clamp of isolated myelinated fibers from the sciatic nerve of acutely uremic rats showed a marked decrease in excitability related to a decrease in the specific Na permeability (P Na) of the nodal membrane. Mean value of the available P Na in the resting node of the uremic rats was 24% of the P Na in a control group. This change explained the decreased nerve conduction velocity in the acutely uremic rat. The Na current reversal potential was decreased in some fibers, reflecting an axoplasmic Na accumulation. The decrease in P Na was to a large extent caused by an increased inactivation, due to a negative shift (about 10 mV) of the steady state inactivation curve along the potential axis. The activation of P Na was similarly shifted (about 10 mV) to a more negative potential region. Such changes may be caused by elevated intracellular [Ca], suggesting a disturbance in Ca metabolism or an intracellular accumulation of cationic metabolites (which possibly have a similar effect) in rats with acute uremia.
Acute Kidney Injury↗
Electrophysiology and morphology of myelinated nerve fibers. IV. Nodal function of pathological nerve fibers.
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Animals↗
Neuropathy-functional abnormalities in the BB rat.
The spontaneously diabetic rat gets a decreased motor-nerve conduction velocity after the onset of diabetes as compared with age- and weight-matched controls. This finding has indicated that these rats develop a neuropathy; but morphological investigations have failed to show structural abnormalities that could explain the decrease in conduction velocity. Measurements of the nervous function revealed a decreased excitability of isolated fibers from sciatic nerves of rats with diabetes duration ranging from 18 days to 6 months. Voltage-clamp analysis of the membrane of the node of Ranvier showed (1) decreased Na-equilibrium potential, reflecting an axoplasmic Na accumulation; (2) decreased specific Na permeability, related both to an increased inactivation of the permeability of the resting node and also a decreased permeability when inactivation had been removed by hyperpolarization of the membrane; and (3) in some nodes a marked increase in the delayed K permeability, which is an early sign of paranodal demyelination. The decrease in Na permeability was the most important factor for the decreased nodal excitability and the decreased conduction velocity. This mechanism may also be involved in the reversible dysfunction found in human diabetic neuropathy.
Action Potentials↗