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Atsuko Mori Hiroyuki Nodera Yoshiko Shibuta Takahiro Okita Hugh Bostock Ryuji Kaji 《Neuroscience letters》2010
Various factors, including maturity, have been shown to influence peripheral nerve excitability measures, but little is known about differences in these properties between axons with different stimulation thresholds. Multiple nerve excitability tests were performed on the caudal motor axons of immature and mature female rats, recording from tail muscles at three target compound muscle action potential (CMAP) levels: 10%, 40% (“standard” level), and 60% of the maximum CMAP amplitude. Compared to lower target levels, axons at high target levels have the following characteristics: lower strength-duration time constant, less threshold reduction during depolarizing currents and greater threshold increase to hyperpolarizing currents, most notably to long hyperpolarizing currents in mature rats. Threshold-dependent effects on peripheral nerve excitability properties depend on the maturation stage, especially inward rectification (Ih), which becomes inversely related to threshold level. Performing nerve excitability tests at different target levels is useful in understanding the variation in membrane properties between different axons within a nerve. Because of the threshold effects on nerve excitability and the possibility of increased variability between axons and altered electric recruitment order in disease conditions, excitability parameters measured only at the “standard” target level should be interpreted with caution, especially the responses to hyperpolarizing currents. 相似文献
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The persistent Na(+) current (Na(p)) in peripheral axons plays an important functional role in controlling the axonal excitability. Abnormal Na(p) is believed to contribute to neurodegeneration and neuropathic pain, and thus it is an attractive therapeutic target. To assess the chronic behavior of selective Na(p) blockade, axonal excitability testing was performed in vivo in normal male mice exposed to ranolazine by recording the tail sensory nerve action potentials (SNAPs). Seven days after administering ranolazine i.p. (50mg/kg) daily for 1 week, nerve excitability testing showed decreased strength-duration time constant in the ranolazine group in comparison to the control (P<0.03). This change is explained by the long-term effects of ranolazine on Na(p). Importantly, ranolazine showed no effect on other ion channels that influence axonal excitability. Further study is needed to assess the chronic Na(p) blockade as a useful therapy in peripheral nerve diseases associated with abnormal nerve excitability. 相似文献
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Persistent Na+ current (Nap) in the peripheral axons play an important functional role in controlling the axonal excitability. Abnormal Nap is believed to contribute to neurodegeneration and neuropathic pain, and thus it is an attractive therapeutic target. To assess the behavior of selective Nap blockade, axonal excitability testing was performed in vivo in 10 normal male mice exposed to ranolazine by recording the tail sensory nerve action potentials (SNAPs). Twenty minutes after administering ranolazine i.p. (50 mg/kg), the following changes were observed: lower SNAP amplitudes and the need for greater stimulus currents; greater threshold changes induced by long hyperpolarizing currents; reduced accommodation to long depolarizing current along with reduced late subexcitability; and reduced strength-duration time constant. These changes are explained by the suppression of Nap leading to greater threshold currents, partial block of transient Na+ current, and suppression of slow K+ currents. The suppressed slow K+ currents appear to limit the modification of the membrane excitability by ranolazine. This study confirms the utility of axonal excitability testing as a useful treatment biomarker in neurological conditions in which Nap function is being modified. 相似文献
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Steven Hageman Maria O. Kovalchuk Boudewijn T.H.M. Sleutjes Leonard J. van Schelven Leonard H. van den Berg Hessel Franssen 《Clinical neurophysiology》2018,129(4):809-814
Objective
Sodium-potassium pump dysfunction in peripheral nerve is usually assessed by determining axonal hyperpolarization following maximal voluntary contraction (MVC) or maximal electrical nerve stimulation. As MVC may be unreliable and maximal electrical stimulation too painful, we assessed if hyperpolarization can also be induced by submaximal electrical nerve stimulation.Methods
In 8 healthy volunteers different submaximal electrical stimulus trains were given to the median nerve at the wrist, followed by 5 min assessment of thresholds for compound muscle action potentials of 20%, 40% or 60% of maximal.Results
Threshold increase after submaximal electrical nerve stimulation was most prominent after an 8?Hz train of at least 5 min duration evoking submaximal CMAPs of 60%. It induced minimal discomfort and was not painful. Threshold increase after MVC was not significantly higher than this stimulus train.Conclusions
Submaximal electrical stimulation evokes activity dependent hyperpolarization in healthy test subjects without causing significant discomfort.Significance
Sodium-potassium pump function may be assessed using submaximal electrical stimulation. 相似文献5.
Yoshiko Shibuta Yoshimitsu Shimatani Hiroyuki Nodera Yuishin IzumiRyuji Kaji 《Clinical neurophysiology》2013,124(10):2046-2053
Objective
Amyotrophic lateral sclerosis (ALS) is characterised by the increased excitability of motoneurons and heterogeneous loss of axons. The heterogeneous nature of the disease process among fibres may show variability of excitability in ALS.Methods
Multiple nerve excitability tests were performed in 28 ALS patients and 23 control subjects, by tracking at the varying threshold levels (10%, 20%, 40% and 60% of maximum amplitudes).Results
In normal controls, excitability measures at low target levels have the following characteristics compared to those at high target levels: longer strength–duration time constant, greater threshold reduction during depolarising currents and smaller threshold increase to hyperpolarising currents. ALS patients had less clear amplitude dependency of the parameters than the controls, indicating variability of axonal excitability. Three ALS patients demonstrated greater target-amplitude-dependent threshold changes in threshold electrotonus than controls, suggesting selective axonal hyperexcitability.Conclusions
Some of the ALS patients had variable axonal excitability at different target amplitudes, suggesting preferential hyperexcitability in the axons with low target amplitude levels.Significance
Variable membrane potentials of motor axons in ALS may be assessed by recording excitability testing at different target amplitude levels. 相似文献6.
Yoshiko Shibuta Hiroyuki Nodera Atsuko Nodera Takahiro Okita Kotaro Asanuma Yuishin Izumi Ryuji Kaji 《Clinical neurophysiology》2010,121(12):2117-2120
Objective
Slow potassium current (IKs) is important in controlling nerve excitability and its impairment is known in various neurological diseases, including amyotrophic lateral sclerosis (ALS). IKs gives rise to the late subexcitability phase of the recovery cycle, which can be amplified by the use of multiple conditioning pulses. The clinical utility of this technique has not previously been explored.Methods
Nerve excitability tests, including recovery cycles with single and double conditioning pulses 4 ms apart (RC and RC2, respectively) were performed in patients with ALS and control subjects. Late subexcitability values obtained by RC and RC2 were compared in both groups.Results
RC2 was well tolerated in all the subjects. The threshold changes in late subexcitability by RC2 were greater than those by RC in both groups (mean (%): RC, 16.0/13.3; RC2, 34.9/29.4 (Control/ALS)). The ALS group showed lower threshold changes than controls by both methods. Statistical analysis between the ALS and control groups provided smaller P value by RC2 (P = 0.018) than by RC (P = 0.046). Also, RC2 provided non-significant, but slightly more distinguishing non-parametric rank analysis and greater Area Under the Curve (AUC) by Receiver Operating Characteristic (ROC). RC2 produced more identifiable single peak for late subexcitability than RC in an ALS patient whose late subexcitability was decreased.Conclusions
Two conditioning stimuli provide greater threshold change for late subexcitability and possibly clearer identification of a peak threshold change than conventional recovery cycle. The findings obtained by this new protocol reinforce the previously reported impairment of IKs in ALS.Significance
Amplification of IKs by double conditioning pulses is applicable in humans and may help elucidating its clinical significance in pathophysiology in neurological diseases. 相似文献
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