Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves.

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten microelectrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.     

Age related skeletal muscle response to electrical stimulation

We hypothesized that the conditioned muscles of elderly and growing organisms have different responses to electrical stimulation from that of young adult organisms. Five day old lambs, 1 year old sheep, and 8 year old elderly sheep were used for this investigation. The latissimus dorsi muscle (LDM) was partially mobilized and left in situ. Two electrodes were implanted and electrical stimulation (ES) was begun for 8 weeks; it was then stopped for 2 weeks. Biopsies were taken before ES, after 8 weeks of ES, and after the 2 week delay period. The LDM of old sheep has less fatigue resistance than the LDM of younger animals. Conditioned LDM of the lamb continued to be fatigue resistant after a 2 week delay compared with adult sheep. In all animals, lactate dehydrogenase (LDH) fraction five decreased and LDH-1 + 2 fractions increased after ES. After a 2 week delay, the data returned to baseline values only in adult animals. The percentage area occupied by mitochondria in old sheep was less after ES than in younger animals. In all animals, the mitochondrial area increased after ES and reverted to baseline values after the delay. The number of nuclei and fibers considerably increased after ES. Only in the lamb did the number of nuclei and fibers continue to be elevated after the delay. There are more changes in young skeletal muscle than in adult (1 year or 8 year old) muscle during ES, and they "remember" these properties. Elderly skeletal muscle does not convert to a fatigue resistant state as completely as adult skeletal muscle during a conventional 8 week ES protocol. It is necessary to change and prolong the ES protocol for elderly patients.     

Characterization and control of muscle response to electrical stimulation

The maintenance of upright posture in neurologically intact human subjects is mediated by two major nervous pathways. The first, leading from the cerebral cortex through the spinal cord to motor neurons, activates muscles which produce postural movements. The second, leading from various sensory organs to higher centers, provides sensory feedback regarding the postural state. The path through the spinal cord is no longer intact in victims of spinal cord injury and loss of normal control of muscle activity results. Functional neuromuscular stimulation (FNS) has been shown as a feasible method for obtaining muscle contraction in paraplegic and has been proposed as a means for control of antero-posterior sway to make upright posture possible for these individuals. Before muscle can be controlled through the use of FNS, the response of muscle to electrical stimulation must be understood. In past studies, linear control theory has been applied to the analysis of this response and to the testing of various controllers. The aim of this study was to demonstrate some control issues in FNS using linear control theory, as it applies to electrical stimulation of muscle for stabilization of posture. The linearity of the muscle response was improved through closed-loop control using pole compensation techniques. The excess phase shift of the system due to the time delay in the muscle response, however, limits the ability to increase the open-loop gain in order to obtain improved performance. A suggestion for further study is the application of this methodology for uses in posture control.     

Non-linearity of skin resistance response to intraneural electrical stimulation of sudomotor nerves

Intraneural electrical stimuli (0.3 mA, 0.2 ms) were delivered via a tungsten micro-electrode inserted into a cutaneous fascicle in the median nerve at the wrist in 16 normal subjects, and the effects on the sweat glands within the innervation zone were recorded as changes of skin resistance. In order to examine the relationship between the skin resistance level and the amplitude of transient resistance responses, trains of high frequency stimulation were used to reduce the skin resistance level and then transient resistance responses were evoked by single stimuli at 0.1 Hz. Regional anaesthesia of the brachial plexus in the axilla eliminated spontaneous sympathetic activity and reflex effects. At high skin resistance levels response amplitudes to single stimuli were low but they increased successively to a maximum at intermediate levels and then decreased again at low resistance levels. Repeated stimulation sequences evoked qualitatively similar response curves but quantitatively both response amplitudes and skin resistance levels were slightly reduced upon repetition. We suggest that the changes of response amplitudes are due to variable resistivity of the corneal layer. The shifts of the response curves with repetition of stimulation may result from increased hydration of the corneum. It is concluded that the variability of response amplitudes to constant stimuli makes the amplitude of a skin resistance response unsuitable as an indicator of the strength of sympathetic sudomotor nerve traffic.     

Glycogen depletion of human skeletal muscle fibers in response to high-frequency electrical stimulation.

The purpose of the present study was to evaluate the pattern of change in muscular glycogen content in response to high-frequency electrical stimulation (HFES). Muscle biopsies were taken from the vastus lateralis muscle of 7 healthy young men before, 15 min after, and 30 min after electrical stimulation delivered at a 50-Hz frequency (15 s on, 45 s off) at an intensity of 100 mA. The glycogen content of type I, IIA, and IIB muscle fibres was evaluated using microphotometry of periodic acid Schiff (PAS) stained fibres. After 15 min of electrical stimulation, the glycogen content in type I, IIA, and IIB muscle fibres significantly decreased from 113 +/- 10 (mean +/- SE) to 103 +/- 10 (p < or = 0.05), 129 +/- 9 to 102 +/- 12 (p < or = 0.01), and 118 +/- 8 to 90 +/- 13 (p < or = 0.01) arbitrary relative units, respectively. No further decrement in glycogen content was observed in all three fibre types following an additional 15 min of HFES. In addition, isometric force decreased by approximately 50%, from 125.9 +/- 20.0 N to 64.2 +/- 7.7 N (p < or = 0.01), during the first 15 contractions. No further decrease in isometric force was observed following an additional 15 contractions of HFES. These results reveal that significant reductions in isometric force of knee extensor muscles and glycogen content of all human skeletal muscle fibre types in vastus lateralis muscle are observable after 15 min of neuromuscular high-frequency transcutaneous electrical stimulation.     

Action potential patterns of isolated frog muscle spindle in response to sinusoidal stimulation

Signal transfer in the isolated frog muscle spindle is investigated using the linear frequency domain analysis technique. Sinusoidal stretches of different amplitudes (20-120 micron) and frequencies (0.1-120 Hz) were applied at different levels of static prestretch, ranging from resting length (L0) up to L0 + 400 micron, so that the frequency-response characteristics were measured at different operating points within the dynamic range. The neuronal responses were recorded from the first node of the afferent stem fiber with a modified air-gap technique. By this means, subthreshold receptor potentials, prepotentials preceding the impulse, and the propagated action potentials were recorded simultaneously, thus providing a detailed insight into the encoding process. There is a well-defined dynamic range of receptor responses. At L0, the encoding site is depolarized to its firing level and discharges spontaneous stimulus-independent impulses. The upper limit is given by the saturation of the receptor potential, which keeps the depolarization maximum below the level of sodium inactivation. Therefore a "depolarization block" or "overstretch" does not exist in the muscle spindle; i.e., the receptor retains its ability to encode information over a large range of dynamic and static displacements. Since the dynamic curves of the receptor potential are not symmetrical about their static operating point, the impulse pattern remains modulated throughout the dynamic range, even if small sinusoids are superimposed on a large static prestretch. The afferent discharge pattern is mainly regulated by the modulated AC component of the receptor potential. At low stimulus frequencies (less than 1 Hz) the receptor potential modulates almost linearly about the mean membrane voltage, so that the evoked discharge pattern displays a smooth analog signal, which is close to sinusoidal. Increasing the static prestretch increases both the peak response and the modulation depth of the impulse pattern. In the intermediate frequency range (1-10 Hz), the cycle histogram disintegrates into discrete peaks separated by empty bins, because the nonlinear receptor potential elicites firmly phase-locked action potentials during its fast depolarization transient. Raising the prestretch level improves the precision of phase locking and increases the number of spikes elicited per cycle.(ABSTRACT TRUNCATED AT 400 WORDS)     

Mechanical response with reversed electrical response to noradrenaline by Ca-deprived arterial smooth muscle

1. When sheep carotid arteries had become electrically active after 30 min in Ca-free saline, noradrenaline 0.1 mM caused almost as much contraction as it did with Ca 1.25 mM present; it also caused slight electrical depolarization, usually with increased spike frequency, followed by electrical quiescence.2. In Ca-free saline with EDTA the arteries became profoundly depolarized, and their mechanical responses greatly reduced, within a few minutes. The mechanical responses to noradrenaline that remained were accompanied by electrical repolarization or, after longer periods in EDTA, by no electrical change.3. This residual mechanical responsiveness to noradrenaline, always tested at 36 degrees C, declined on average 26 times as rapidly during exposure to EDTA at 36 degrees C as at 5 degrees C and was not reduced by increasing the concentration of EDTA from 1.25 to 12.5 mM. This temperature-sensitivity was significantly too high to be explained by a diffusion-limited process.4. The results suggest that most of the tissue Ca responsible for contractility in simple Ca-free saline was either free in the extracellular space or in cellular stores that were discharged within a few minutes when free extracellular Ca was removed. They also indicate a small resistant Ca store which did not communicate with the exterior by diffusion, and part of which noradrenaline could utilize for contraction by means not dependent on depolarization conducted from the cell membrane.     

Mechanical and electrical responses modulated by excitation of inhibitory nerves during stimulation with high-potassium solutions in circular smooth muscle of the rabbit rectum.

The properties of the mechanical responses produced by solutions containing high concentrations of potassium ion (high-K solution, [K(+)](o) = 9-27 mM) were investigated in circular smooth muscle preparations isolated from the rabbit rectum. Isometric recording of mechanical responses of the muscle revealed spontaneous contractions, which successively decreased and finally disappeared in most preparations. Stimulation of the smooth muscle with high-K solutions elicited an increase in both amplitude and frequency of twitch contractions (sustained component), with about a 2 min delay in the beginning (initial inhibition), and a transient large contraction shortly after the cessation of stimulation (after contraction). Transmural nerve stimulation (TNS) with electrical pulses for 1 min at 1 Hz frequency produced a sustained inhibition, but a transient contraction followed after termination of TNS. In the presence of tetrodotoxin (TTX), the TNS-induced responses were abolished, while a high-K solution elicited increased twitch contractions with a short delay and abolished the after contraction. Suramin produced effects similar to TTX on the responses produced by high-K solutions or TNS, but this was not the case for atropine, guanethidine or N(omega)-nitro-L-arginine (L-NA). Recording membrane potentials with microelectrodes revealed that TNS evoked an inhibitory junction potential (i.j.p.) which was non-adrenergic, non-cholinergic and non-nitrergic in nature. High-K solutions elicited a tri-phasic change in the membrane potential; an initial hyperpolarization, followed by a sustained depolarization and finally a transient depolarization on cessation of high-K stimulation. TTX or suramin inhibited the i.j.p.s and altered the tri-phasic change in the membrane potential produced by a high-K solution to a mono-phasic depolarization. No significant modulation of electrical responses of the membrane induced by TNS or high-K solution was elicited by atropine, guanethidine or L-NA. The results indicated that the circular smooth muscle of the rabbit rectum is innervated by inhibitory nerves, and that stimulation with high-K solutions caused inhibitory neuronal modulation of both electrical and mechanical responses of the smooth muscle, in a suramin-sensitive way.     

Responses of intradental nerves to electrical and thermal stimulation of teeth in dogs.

1. Experiments were carried out to investigate the mechanism whereby thermal stimul excite nerves to produce pain from teeth. 2. Recordings have been made from single fibres dissected from the inferior dental nerve in dogs during thermal stimulation of the lower canine tooth. 3. In preliminary experiments, no units were found with thresholds close to the thresholds for pain in man (45 and 27 degrees C) and subsequently test stimuli of 55 degrees C, applied for up to 15 sec, and 0-5 degrees C were used. 4. Of 117 fibres tested, forty-three responded to cooling but not to heating and nine responded to heating but not to cooling. 5. By applying thermal stimuli direct to the saphenous nerve in cats, it was shown that these responses might have been due to direct excitation of nerves and not to stimulation of specialized receptors. 6. Some units responded to electrical stimulation of the tooth pulp with a latency which decreased abruptly at a critical intensity as the stimulus was increased above threshold. Evidence was obtained which suggested that this was due to branching of the fibres.     

Calcium spike induced by electrical stimulation to the sensory nerve terminal of the frog muscle spindle

A calcium spike in the sensory nerve terminal of the frog muscle spindle could be elicited by electrical pulses, which were given across an air-gap on which the first myelinated segment of the parent axon outside the spindle capsule was bridged, after the sodium spike had been blocked by treatment with tetrodotoxin (TTX). The threshold current was 1.1-2.4 nA higher than that for the sodium spike, suggesting that the calcium channels distribute distally to the site of afferent impulse initiation, or that the density of calcium channels on the encoding site may be less than that along portions distal to the site.     

Rebound excitation of the smooth muscle cells of the guinea-pig taenia coli after stimulation of intramural inhibitory nerves

1. A study has been made of the increase in the rate of action potential firing in spontaneously active cells and of the initiation of action potential firing in quiescent cells of the taenia coli after stimulation of the intramural inhibitory nerves.2. In the majority of cells which fired action potentials spontaneously at intervals of about 1 sec, stimulation of the intramural inhibitory nerves with single pulses gave an inhibitory junction potential (I.J.P.) which was followed by action potentials which occurred at intervals as small as 0.5 sec. The increased rate of firing lasted up to 30 sec.3. A small number of cells were either not spontaneously active or only fired action potentials at intervals greater than 5 sec. After stimulation of the intramural inhibitory nerves with either single or repetitive pulses, the quiescent cells gave I.J.P.S which were followed by either a single action potential or a burst of action potentials.4. The rate of firing of action potentials after an I.J.P., and the duration of this enhanced rate of firing increased with an increase in the mean amplitude of the hyperpolarization during the I.J.P. As the amplitude of the I.J.P. increases with an increase in frequency of stimulation of the nerves, the rebound excitation increases with an increase in the frequency of stimulation of the inhibitory nerves.     

Transmission from intramural inhibitory nerves to the smooth muscle of the guinea-pig taenia coli

1. Membrane potential changes of smooth muscle cells were recorded during stimulation of the intramural inhibitory nerves to the taenia coli.2. Stimulation across the taenia coli with single pulses of 200 musec duration excites the intramural nerves and not the muscle directly.3. The membrane potential changes due to stimulation of the intramural inhibitory nerves were different from those produced by perivascular inhibitory nerve stimulation in the following ways: hyperpolarizations (i.j.p.'s) of up to 25 mV were produced in response to single pulses; the latency, i.e. the time taken for the membrane to hyperpolarize after a stimulus of maximal strength, was as short as 80 msec; when the nerves were stimulated repetitively the membrane was hyperpolarized by up to 35 mV and all spontaneous activity was abolished; the mean hyperpolarization due to repetitive stimulation increased with the frequency of stimulation up to 10 pulses/sec and then remained constant; the hyperpolarization due to stimulation at frequencies greater than 5 pulses/sec was not maintained but decreased after 3-5 sec of stimulation; and finally when stimulation had ceased action potentials commenced firing at frequencies greater than normal.4. The amplitude and rate of hyperpolarization of the i.j.p. increased with increasing strength of stimulation until a maximum amplitude and rate of hyperpolarization was reached. The recovery or depolarizing phase of the i.j.p. was exponential with a time constant which varied from about 250 msec to 500 msec and could not therefore be due to the discharge of the membrane capacitance. In some cases there was an inflexion on this depolarizing phase and in these cases recovery led directly into an action potential.5. Spontaneous hyperpolarizations of the membrane were seen in some cells, and these hyperpolarizations were similar to those recorded on submaximal stimulation of the intramural nerves.6. There were no changes in the characteristics of the i.j.p. in the presence of guanethidine or bretylium.     

Responses of primate spinothalamic tract neurons to electrical stimulation of hindlimb peripheral nerves.

The responses of spinothalamic tract neurons were studied by extra- and intracellular recordings from the lumbosacral spinal cord in anesthetized rhesus monkeys (Macaca mulatta). The neurons were identified by antidromic activation from the contralateral diencephalon. They were then classified by the mildest form of mechanical stimulation applied to the ipsilateral hindlimb. The effects of electrical stimulation of the nerve(s) supplying the receptive field were investigated. Graded electrical stimulation revealed that the threshold responses of spinothalamic tract neurons excited by weak mechanical stimuli occurred when the largest afferent fibers were activated. On the other hand, neurons that required intense mechanical stimulation for their excitation tended to have higher thresholds to electrical stimulation. Some spinothalamic tract cells were shown to receive monosynaptic excitatory connections from peripheral nerve fibers, although polysynaptic connections may generally be more important. An input from unmyelinated afferent fibers was demonstrated. It is concluded the primate spinothalamic tract neurons receive a rich convergent input from a variety of cutaneous receptors. The experiments provide some evidence for the most likely types of receptors.