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  • 1
    ISSN: 1432-0428
    Keywords: adenosine triphosphatase ; diabetic neuropathies ; galactosaemia ; myo-inositol ; polyol pathway ; streptozotocindiabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study measured the ouabain-sensitive adenosine triphosphatase activity in sciatic nerve, lumbar dorsal root ganglia and superior cervical ganglia from control rats, rats with 8 weeks streptozotocin-induced diabetes and rats fed a diet containing 20% galactose for 8 weeks. Whilst the sciatic nerves of the diabetic rats showed a 42% reduction in ouabain-sensitive adenosine triphosphatase activity, the galactose-fed rats showed an increase of 124% (p〈0.01 and p〈0.005, respectively, compared to controls). There was also a reduction (by 30% compared to controls; p〈0.05) in the ouabain-sensitive adenosine triphosphatase activity of the dorsal root ganglia from the diabetic rats, but their superior cervical ganglia did not show a significant fall. The ganglia of the galactosaemic rats showed no change in ouabain-sensitive adenosine triphosphatase activity compared to controls. These changes coexisted with increases in appropriate polyol pathway metabolites in all tissues of both diabetic and galactosaemic rats. There were also depletions of myo-inositol in the sciatic nerves and dorsal root ganglia of diabetic and galactosaemic rats, but their superior cervical ganglia contained levels of myo-inositol which were similar to those of controls. The nerves of the galactosaemic rats showed increased water content; the nerves of the diabetic rats did not. The data argue against a simple relationship between myoinositol depletion and impaired Na/K adenosine triphosphatase activity in association with exaggerated polyol pathway flux in peripheral nervous tissue.
    Type of Medium: Electronic Resource
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  • 2
    ISSN: 1432-0428
    Keywords: Adenosine triphosphatase ; aldose reductase ; diabetic neuropathies ; galactosaemia ; myo-inositol ; polyol pathway ; streptozotocin diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study measured the ouabain-sensitive and ouabain-resistant adenosine triphosphatase activity in homogenates of the sciatic nerves and of pooled fourth and fifth lumbar dorsal root ganglia from rats fed 20% galactose or made diabetic with streptozotocin for either 4 or 8 weeks. Diabetes caused reductions in both fractions of sciatic nerve adenosine triphosphatase activity. After 8 weeks the ouabainsensitive fraction was 54% of control (p〈0.05) and the ouabain-resistant fraction was 57% of control (p〈0.05). Galactose feeding more than doubled the ouabain-sensitive adenosine triphosphatase activity in the sciatic nerve (225% of control after 4 weeks, 215% of control after 8 weeks of galactose feeding, bothp〈0.01) and produced a progressive increase in the ouabain-resistant fraction (119% of control at 4 weeks (p〈0.05) and 176% of control at 8 weeks (p〈0.01)). In a group of rats fed galactose for 5 days, sciatic nerve ouabain-sensitive adenosine triphosphatase activity was 165% of control. Treatment with the aldose-reductase inhibitors tolrestat, ponalrestat or sorbinil prevented accumulation of polyol and depletion of myo-inositol in the sciatic nerves, indicating effective inhibition of aldose reductase. These drugs prevented completely the effect of galactose on the sciatic nerve adenosine triphosphatase activity, but had no significant effect on the reduction in adenosine triphosphatase activity in the sciatic nerves of diabetic rats. In the dorsal root ganglia galactose feeding had no measurable effect on the adenosine triphosphatase activity. Diabetes caused a modest numerical reduction in the ouabain-sensitive activity only. The findings indicate markedly different effects of diabetes and galactosaemia on the adenosine triphosphatase activity in rat sciatic nerve and show that the reduction in activity seen in the nerves of diabetic rats was not related to exaggerated polyol pathway flux.
    Type of Medium: Electronic Resource
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  • 3
    ISSN: 1432-0428
    Keywords: Axonal flow ; diabetic neuropathies ; hypothermia ; motor neurones ; streptozotocin-diabetes
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Summary This study measured the velocity of fast orthograde axonal transport of incorporated 3H-proline in motoneurones of the sciatic nerve in control rats and in rats with streptozotocin-induced diabetes of 3 weeks duration. Sciatic nerve and abdominal cavity temperatures were monitored throughout the period of measurement of transport velocity, and the rats were warmed to minimise hypothermia at both sites. There was marked abdominal and sciatic nerve hypothermia immediately after operation, and this effect was more intense in diabetic rats than in control rats. In steady state, abdominal cavity temperature (mean±SEM) was 38.1±0.1 °C in both control and diabetic rats, and the sciatic nerve temperatures were 37.8±0.1 °C in controls and 37.1±0.3 °C in diabetic rats. The difference was not statistically significant. The velocities of orthograde axonal transport for the fastest molecules containing 3H-proline were 14.0±0.9 (SEM)mm/h for controls and 13.9±1.1 (SEM)mm/h for diabetic rats. Thus, no velocity difference was observed. The findings are discussed in relation to measurements of fast orthograde transport velocity in experimental diabetes in other studies. It is suggested that, where velocity deficits have been seen in diabetic rats, nerve hypothermia should be considered as a contributory factor.
    Type of Medium: Electronic Resource
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  • 4
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 422 (1993), S. 354-363 
    ISSN: 1432-2013
    Keywords: K+ channel inactivation ; N-type inactivation ; C-type inactivation ; Pore or P-type inactivation ; External TEA enhancement of current ; External K+ enhancement of current ; Conductance ; Pore mutations
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract An N-terminus peptide or a C-terminus mechanism involving a single residue in transmembrane segment 6 produces inactivation in voltage-dependent K+ channels. Here we show that a single position in the pore of K+ channels can produce inactivation having characteristics distinct from either N- or C-type inactivation. In a chimeric K+ channel (CHM), the point reversion CHM V 369I produced fast inactivation and CHM V 369S had the additional effect of halving K+ conductance consistent with a position in the pore. The result was not restricted to CHM; mutating position 369 in the naturally occurring channel Kv2.1 also produced fast inactivation. Like N- and C-types of inactivation, pore or P-type inactivation was characterized by short bursts terminated by rapid entry into the inactivated state. Unlike C-type inactivation, in which external tetraethylammonium (TEA) produced a simple blockade that slowed inactivation and reduced currents, in P-type inactivation external TEA increased currents. Unlike N-type inactivation, internal TEA produced a simple reduction in current and K+ occupancy of the pore had no effect. External TEA was not the only cation to increase current; external K+ enhanced channel availability and recovery from inactivation. Additional features of P-type inactivation were residue-specific effects on the extent of inactivation and removal of inactivation by a point reversion at position 374, which also regulates conductance. The demonstration of P-type inactivation indicates that pore residues in K+ channels may be part of the inactivation gating machinery.
    Type of Medium: Electronic Resource
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  • 5
    Electronic Resource
    Electronic Resource
    Springer
    Cellular and molecular neurobiology 3 (1983), S. 381-395 
    ISSN: 1573-6830
    Keywords: Ca current ; voltage clamp ; ATP ; snail neuron
    Source: Springer Online Journal Archives 1860-2000
    Topics: Biology
    Notes: Summary 1. Ca currents were examined with regard to their recovery from inactivation. The experiments were done on isolated nerve cell bodies ofHelix aspersa using a combined suction pippet, microelectrode method for voltage clamp, and internal perfusion. Ca currents were separated by suppressing K and Na currents. 2. The time course of recovery was determined by applying a test pulse at intervals ranging from 1 msec to 20 sec after prepulses varying from 20 to 3000 msec in duration. Each pair of pulses was preceded by a control pulse to ensure that the Ca currents had recovered before the next test pair was applied. Ba and Ca currents were compared and the effects of intracellular perfusion with EGTA, ATP, and vanadate were examined. 3. Ba currents recovered in two stages and this time course was well fit by a sum of two exponentials with amplitudes and time constants given byA 1 andτ 1 for the fast component andA 2 andτ 2 for the slow component. In Ba the time constants were unchanged when prepulse durations were prolonged from 70 to 700 msec, although the initial amplitudesA 1 andA 2, particularlyA 2, were increased. 4. Comparable influxes of Ca during the prepulse caused much more inactivation, but interestingly the recovery occurred at the same rate. The time course of Ca current recovery was also fit by a sum of two exponentials, the time constants of which were both smaller than the time constants of Ba current recovery. However, the time constants of Ca current recovery were increased markedly when prepulse durations were prolonged. Increasing the extracellular Ca concentration had a similar effect. 5. Increasing the Ba influx had no effect on the recovery time constants, and the Ba results are consistent with reversible inactivation gating of potential-dependent membrane Ca channels. The Ca results show that Ca influx enhances inactivation. Intracellular perfusion with EGTA resulted in less inactivation in the cast of Ca but it had no effect on Ba currents. Intracellular ATP increased the rate of recovery of Ca currents, and intracellular vanadate inhibited recovery. It is concluded that recovery of Ca channels depends upon both Ca influx and membrane potential and is modulated by agents which affect Ca metabolism.
    Type of Medium: Electronic Resource
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