scholarly journals In Vivo Electrophysiological Measurement of the Rat Ulnar Nerve with Axonal Excitability Testing

Author(s):  
Brandon M. Wild ◽  
Renée Morris ◽  
Mihai Moldovan ◽  
Christian Krarup ◽  
Arun V. Krishnan ◽  
...  
2019 ◽  
Vol 90 (e7) ◽  
pp. A4.1-A4
Author(s):  
Michelle A Farrar ◽  
Susan E Tomlinson ◽  
James Howells ◽  
Cindy Shin-YI Lin ◽  
Kate Carey ◽  
...  

IntroductionMutations in SCN1A encoding the Nav1.1 subunit of the neuronal sodium channel underlie the devastating epilepsy of Dravet’s syndrome.1 The mechanism by which Nav1.1 dysfunction causes seizures is not clear. In vitro and in silico channel evaluation can support mutation pathogenicity but cannot define the in vivo impact of channel dysfunction. Axonal excitability studies can show the pattern of single-channel dysfunction in disorders where the channel is peripherally expressed.2 This study was undertaken to determine whether axonal excitability studies could detect changes in Dravet’s patients related to the condition or due to medication effect.MethodsPatients with Dravet’s syndrome were recruited from clinics in Sydney and Melbourne and axonal excitability studies were performed. Excitability results were analysed in 3 age groups and compared to age-matched normal controls.ResultsTwenty six patients (ages 2–46) were studied. Findings were most pronounced in patients aged 20–46 (n=7) with 6.9% greater increase in threshold during hyperpolarization(p=0.1), 7.6% greater threshold decrease on depolarization(p=0.005) and, in the recovery cycle, 19.7% reduction in superexcitability(p=0.002) and 26% reduction in subexcitability(p=0.03). Axonal excitability studies resembled previously published changes seen in patients with sodium channel blockade caused by acute tetrodotoxin poisoning.3ConclusionsChanges in excitability of axonal membrane in Dravet’s syndrome are consistent with a decrease in sodium channel function. As the affected channel in Dravet’s syndrome is not peripherally expressed, the effect seen is likely due to the heavy anticonvulsant regime required to control epilepsy, combined with a progressive loss of sodium channel function that occurs with age.ReferencesMeisler MH, O’Brien JE, Sharkey LM. Sodium channel gene family: epilepsy mutations, gene interactions and modifier effects. J Physiol 2010;588:1841–1848.Tomlinson SE, Howells J, Burke D. In vivo assessment of neurological channelopathies: Application of peripheral nerve excitability studies. Neuropharmacology. 2018 Apr;132:98–107.Kiernan MC, Isbister GK, Lin CS, Burke D, Bostock H. Acute tetrodotoxin-induced neurotoxicity after ingestion of puffer fish. Ann Neurol 2005;57:339–48.


2007 ◽  
Vol 22 (7) ◽  
pp. 774-779 ◽  
Author(s):  
Andrew Dilley ◽  
Catherine Summerhayes ◽  
Bruce Lynn

Sensors ◽  
2021 ◽  
Vol 22 (1) ◽  
pp. 58
Author(s):  
Felipe Rettore Andreis ◽  
Benjamin Metcalfe ◽  
Taha Al Muhammadee Janjua ◽  
Winnie Jensen ◽  
Suzan Meijs ◽  
...  

Decoding information from the peripheral nervous system via implantable neural interfaces remains a significant challenge, considerably limiting the advancement of neuromodulation and neuroprosthetic devices. The velocity selective recording (VSR) technique has been proposed to improve the classification of neural traffic by combining temporal and spatial information through a multi-electrode cuff (MEC). Therefore, this study investigates the feasibility of using the VSR technique to characterise fibre type based on the electrically evoked compound action potentials (eCAP) propagating along the ulnar nerve of pigs in vivo. A range of electrical stimulation parameters (amplitudes of 50 μA–10 mA and pulse durations of 100 μs, 500 μs, 1000 μs, and 5000 μs) was applied on a cutaneous and a motor branch of the ulnar nerve in nine Danish landrace pigs. Recordings were made with a 14 ring MEC and a delay-and-add algorithm was used to convert the eCAPs into the velocity domain. The results revealed two fibre populations propagating along the cutaneous branch of the ulnar nerve, with mean velocities of 55 m/s and 21 m/s, while only one dominant fibre population was found for the motor branch, with a mean velocity of 63 m/s. Because of its simplicity to provide information on the fibre selectivity and direction of propagation of nerve fibres, VSR can be implemented to advance the performance of the bidirectional control of neural prostheses and bioelectronic medicine applications.


2017 ◽  
Vol 67 (3) ◽  
pp. 293-307 ◽  
Author(s):  
Seçkin Tuncer ◽  
Tülay Tuncer Peker ◽  
İlksen Burat ◽  
Erhan Kiziltan ◽  
Barkin İlhan ◽  
...  

Abstract In this study, effects of the long-acting amide-type local anesthetic levobupivacaine on axonal conduction and excitability parameters of the rat sciatic nerve were thoroughly examined both in vitro and in vivo. In order to deduce its effects on isolated nerve conduction, compound nerve action potential (CNAP) recordings were performed using the suction method over sciatic nerves of Wistar rats before and after administration of 0.05 % (1.7 mmol L−1) levobupivacaine. Levobupivacaine caused complete CNAP area and amplitude depression by blocking conduction in a time-dependent manner. To assess the influence of levobupivacaine on in vivo excitability properties, threshold-tracking (TT) protocols were performed at sciatic nerves of rats injected with perineural 0.05 % (1.7 mmol L−1) levobupivacaine or vehicle alone. Charge-duration TT results revealed that levobupivacaine increases the rheobase and decreases the strength-duration time constant, suggesting interference of the anesthetic with the opening of Na+ channels. Twenty and 40 % threshold electrotonus curves were found for both groups to follow the same paths, suggesting no significant effect of levobupivacaine on K+ channels for either the fastest or relatively slow conducting fibers. Current-threshold relationship results revealed no significant effect on axonal rectifying channels. However, according to the results of the recovery cycle protocol yielding the pattern of excitability changes following the impulse, potential deviation was found in the recovery characteristics of Na+ channels from the absolute refractory period. Consequently, conduction blockage caused by levobupivacaine may not be due to the passive (capacitive) properties of axon or the conductance of potassium channels but to the decrease in sodium channel conductance.


2016 ◽  
Vol 116 (2) ◽  
pp. 322-335 ◽  
Author(s):  
James Howells ◽  
Hugh Bostock ◽  
David Burke

Human axons in vivo were subjected to subthreshold currents with a threshold impedance amplitude profile to allow the use of frequency domain techniques to determine the propensity for resonant behavior and to clarify the relative contributions of different ion channels to their low-frequency responsiveness. Twenty-four studies were performed on the motor and sensory axons of the median nerve in six subjects. The response to oscillatory currents was tested between direct current (DC) and 16 Hz. A resonant peak at ∼2–2.5 Hz was found in the response of hyperpolarized axons, but there was only a small broad response in axons at resting membrane potential (RMP). A mathematical model of axonal excitability developed using DC pulses provided a good fit to the frequency response for human axons and indicated that the hyperpolarization-activated current Ihand the slow potassium current IKsare principally responsible for the resonance. However, the results indicate that if axons are hyperpolarized by more than −60% of resting threshold, the only conductances that are appreciably active are Ihand the leak conductance, i.e., that the activity of these conductances can be studied in vivo virtually in isolation at hyperpolarized membrane potentials. Given that the leak conductance dampens resonance, it is suggested that the −60% hyperpolarization used here is optimal for Ih. As expected, differences between the frequency responses of motor and sensory axons were present and best explained by reduced slow potassium conductance GKs, up-modulation of Ih, and increased persistent Na+current INaP(due to depolarization of RMP) in sensory axons.


Nano LIFE ◽  
2010 ◽  
Vol 01 (01n02) ◽  
pp. 45-62 ◽  
Author(s):  
JIA GENG ◽  
ANNE P. VONDERHEIDE

Nanobiotechnology entails the use of nanosized materials to build structures that can be applied in both biotechnology and medicine. In one vein of this field of study, scientists seek to mimic the wide variety of nanomachines and macromolecular structures that exist in nature and to replicate them in both structure and function. As a most intriguing example, the bacterial virus phi29 uses a self-contained nanomotor to package its DNA after replication. The 30-nm nanomotor contains 12 copies of a protein (gp10) which together form a 3.6-nm central channel through which the genomic DNA passes into the procapsid during viral assembly and exits during infection. This connector has been recently reengineered and embedded into a lipid bilayer, creating a system with tremendous application for DNA detection and characterization through electrophysiological measurement. A second component of the phi29 bacteriophage is an ATP-binding pRNA that forms a hexameric ring to gear the motor. The pRNA has been utilized to construct nanoparticles of dimers, trimers, hexamers and patterned superstructures via the interaction of two interlocking loops. Such structures constructed via bottom-up assembly have been used in the delivery of drugs, siRNA, ribozymes, and genes to specific cells, both in vitro and in vivo. This review summarizes current studies on the structure, function, and mechanism of the phi29 DNA packaging motor, as well as addresses the applications of these motor components in the field of nanobiotechnology.


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