Neuromuscular current stimulators

Neuromuscular Current Stimulator with High-CompUance Voltage. 288... 

Neuromuscular electrical stimulation is one of the most currently used therapies because it can improve the muscle condition. Low-flow frequencies are applied up to 150 impulses per second and used to reinforce different muscle groups. The muscles are stimulated and activated by short electric impulses so a muscle contraction is realized in the targeted muscle. Treatment goals have to be established at the beginning of the treatment and there are three of them are the muscles moderately or strongly weakened, is there a moderate or bad muscle condition, or is a reduction of a spasticity demanded. 

The basis for the lack of response to 3,4-DAP by the other serotypes is not well understood. At a functional level, serotype A-intoxicated neuromuscular junctions undergo an attenuated but synchronous release of ACh following stimulation preparations intoxicated by serotypes B, D, and F produce asynchronous release where the ACh quanta are dispersed and cannot summate to produce suprathreshold EPPs (Lundh et al., 1977 Molgo et al., 1980 Thesleff, 1989). It is readily apparent that the lack of synchrony would prevent 3,4-DAP from restoring transmitter release however, the factors that lead to asynchronous release are not currently understood. 

Neuromuscular Stimulation. Based on a method that has remained unchanged for decades, electrodes are placed within the excitable tissue that provide current to activate certain pathways. This supplements or replaces lost motor or autonomic functions in patients with paralysis. An example is application of electrical pulses to peripheral motor nerves in patients with spinal cord injuries. These pulses lead to action potentials that propagate across neuromuscular junctions and lead to muscle contraction. Coordinating the elicited muscle contractions ultimately reconstitutes function. 

To assess the effect of drugs on a neuromuscular synapse, either the endplate potentials or the intensity of muscular contractions in response to rhythmic electric stimulation of the nerve are registered In the first case, the evoked gradual responses of the neuromuscular junctions are recorded by means of thin electrodes. Changes in the magnitude of these responses are criteria of the efficiency of the drugs with respect to naptic transmission. In the second case, the facilitation or inhibition of synaptic transmission is reflected by either an increase or a decrease in the intensity of muscular contractions. For convenience, the latter are usually transformed into corresponding oscillations of electric current. 

Figure 15.2. Drosophila larval neuromuscular junction system. A wandering third-instar larva is dissected open to reveal the ventral neuromusculature (see Figure 15.1). The peripheral nerve is severed and stimulated with a glass suction electrode. The muscle is recorded from in two-electrode voltage-clamp (TEVC) configuration. The postsynaptic excitatory junctional current (EJC) is recorded to assay synaptic transmission bottom inset). Top inset) Basis of synaptic transmission event being evoked by nerve stimulation and recorded via ion flux through muscle glutamate receptors.

Histrionicotoxins antagonize both acetylcholine and glutamate-elicited excitation of central neurons (755), and have been cited as antagonizing glutamate-responses in invertebrate muscles (245). Histrionicotoxin also has a depressant effect on spontaneous activity of cortical and spinal neurons (114, 155). Perhydrohistrionicotoxin at very low concentrations (<0.1 pM) blocks endplate currents elicited by iontophoretic acetylcholine in rat neuromuscular preparations, while having no effect on spontaneous miniature endplate currents or endplate currents evoked by nerve stimulation (6, 14). Further studies will be required to clarify the reason for the remarkable potency of perhydrohistrionicotoxin versus responses to ionto-phoretically applied acetylcholine. 

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