Measurement of fasciculations as motor nerve ending discharges in the rat: a dose related effect of neostigmine

The muscle fasciculations caused by neostigmine and similar agents are the result of a primary drug action on motor nerve endings. Asynchronous, repetitive firing of action potentials are evoked at motor nerve endings which are then transmitted to muscle. A dose-response relationship between neostigmine dose and the rate of/or total neural activity has been established in the rat. This fasciculatory response to neostigmine can serve as an index of motor nerve ending excitability and may be useful in assessing the effects of certain pathological states or drug actions at the neuromuscular junction.     

Directed attention influence on the human brain potentials under conditions of probability visual stimulation

Saccadic latency and averaged EEG-potentials connected with switching on of the set and cue visual stimuli were examined in 12 right-handed healthy subjects in M. Posner's "cost-benefit" experimental paradigm. It was shown that attention was reflected in parameters of positive potential P100 evoked by switching on of set and cue stimuli and P300 and slow positive wave PMP1 evoked by switching on of the set stimulus in the relevant conditions. The spatiotemporal pattern of P100 probably reflects the involvement of the frontoparietal network of spacial attention in the perception of a relevant stimulus. Prevalence of the P300 and PMP1 potentials in the right parietal cortex suggests that these potentials reflect processes of space attention and visual fixation. Late positive potentials in a 600-900-ms interval after switching on of the set stimulus were found. Their amplitude was higher in backward averaging and they were predominantly localized in the left frontal cortex. These findings suggest that the late potentials reflect the anticipation and motor attention processes.     

Subunits in quantal transmission at the mouse neuromuscular junction: tests of peak intervals in amplitude distributions

The regular spacing of peaks throughout the amplitude distribution of miniature end-plate potentials, quantal evoked end-plate potentials and quantal currents was demonstrated using autocorrelations and power density spectra calculated from the number of events in the successive bins of the histograms built by Matteson et al. (1979), Kriebel & Florey (1983) and Erxleben & Kriebel (1984). At the same mouse neuromuscular junction, the calculated interpeak was constant for evoked and spontaneous quantal releases, throughout sequential sampling and after change of bin size. The presence of regular peak intervals supports the hypothesis that quantal potentials are composed of potential subunits the size of the smallest subminiature potential. Challenging the hypothesis of an acetylcholine quantum composed of acetylcholine subunits, a postsynaptic origin of the subunit is proposed on the basis of the spatial arrangement in rows of the ACh receptors. The ACh-saturating patch evoked by a quantum release (Land et al., 1980, 1981) activates 10-20 rows of receptors, which is roughly the number of subunits composing a quantal event. Therefore the position of the ACh patch or the continuous variations in its size might cause stepwise variations in the total number of ACh receptors activated by an ACh quantum.     

Effect of acetylcholine on ion transport in the frog skeletal muscle

1. The effect of acetylcholine (ACh) on the ion transport of frog (Rana esculenta) sartorius muscles was studied. ACh was applied in bathing solution, Na influx and K efflux were measured using 24Na and 42K isotopes. 2. Na influx of sartorius muscles was increased by 1 mmol/1 ACh 2-10 fold depending on the experimental arrangement. The increase was greater if Na influx was measured at the beginning of ACh depolarization. During ACh treatment the Na influx took about the same time course as the depolarization recorded extracellularly. This type of recording approximately reflects the depolarization proceeding on the sartorius muscle fibres. 3. The presence of 31 nmol/l tetrodotoxin (TTX) did not modify the degree of increase of Na influx. 4. Rate coefficients for K efflux were increased 2-5 fold by ACh. The maximum rate coefficients were obtained in the first minute of ACh treatment. 5. Increase in K loss evolves also in the presence of 31 nmol/l TTX. The increase in rate coefficients was found to be about 30% less than without TTX in the first minute of ACh action. 6. The results indicate that in the presence of ACh the observed increase in Na influx and K efflux is brought about mainly by changes in Na and K conductance induced by ACh at the end-plates rather than by the action potentials accompanying ACh depolarization.     

Key role of the nicotinic receptor in neurotransmitter exocytosis in human chromaffin cells

The whole-cell secretory response evoked by acetylcholine (ACh) in human chromaffin cells was examined using a new protocol based on quickly switching from the voltage-clamp to the current-clamp (CC) configuration of the patch-clamp technique. Our experiments revealed that Ca(2+) entry through the nicotinic receptor at hyperpolarized membrane potentials contributed as much to the exocytosis (100.4 +/- 27.3 fF) evoked by 200 ms pulses of ACh, as Ca(2+) flux through voltage-dependent Ca(2+) channels at depolarized membrane potentials. The nicotinic current triggered a depolarization event with a peak at +49.3 mV and a 'plateau' phase that ended at -23.9 mV, which was blocked by 10 mumol/L mecamylamine. When a long ACh stimulus (15 s) was applied, the nicotinic current at the end of the pulse reached a value of 15.45 +/- 3.6 pA, but the membrane potential depolarization still remained at the 'plateau' stage until withdrawal of the agonist. Perfusion with 200 mumol/L Cd(2+) during the 15 s ACh pulse completely abolished the plasma membrane depolarization at the end of the pulse, indicating that Ca(2+) entry through Ca(2+) channels contributed to the membrane potential depolarization provoked by prolonged ACh pulses. These findings also reflect that voltage-dependent Ca(2+) channels were recruited by the small current flowing through the desensitized nicotinic receptor to maintain the depolarization. Finally, muscarinic receptor activation triggered a delayed exocytotic process after prolonged ACh stimulation, dependent on Ca(2+) mobilization from the endoplasmic reticulum. In summary, we show here that nicotinic and muscarinic receptors contribute to the exocytosis of neurotransmitters in human chromaffin cells, and that the nicotinic receptor plays a key role in several stages of the stimulus-secretion coupling process in these cells.     

Conduction of hyperpolarization along hamster feed arteries: augmentation by acetylcholine

The conduction of vasodilation along resistance vessels has been presumed to reflect the electrotonic spread of hyperpolarization from cell to cell along the vessel wall through gap junction channels. However, the vasomotor response to acetylcholine (ACh) encompasses greater distances than can be explained by passive decay. To investigate the underlying mechanism for this behavior, we tested the hypothesis that ACh augments the conduction of hyperpolarization. Feed arteries (n = 23; diameter, 58 +/- 4 microm; segment length, 2-8 mm) were isolated from the hamster retractor muscle, cannulated at each end, and pressurized to 75 mmHg (at 37 degrees C). Vessels were impaled with one or two dye-containing microelectrodes simultaneously (separation distance, 50 microm to 3.5 mm). Membrane potential (E(m)) (rest, approximately -30 mV) and electrical responses were similar between endothelium and smooth muscle, as predicted for robust myoendothelial coupling. Current injection (-0.8 nA, 1.5 s) evoked hyperpolarization (-10 +/- 1 mV; membrane time constant, 240 ms) that conducted along the vessel with a length constant (lambda) = 1.2 +/- 0.1 mm; spontaneous E(m) oscillations (approximately 1 Hz) decayed with lambda = 1.2 + 0.1 mm. In contrast, ACh microiontophoresis (500 nA, 500 ms, 1 microm tip) evoked hyperpolarization (-14 +/- 2 mV) that conducted with lambda = 1.9 +/- 0.1 mm, 60% further (P < 0.05) than responses evoked by purely electrical stimuli. These findings indicate that ACh augments the conduction of hyperpolarization along the vessel wall.     

Influence of segmental and extra-segmental conditioning stimuli on cortical potentials evoked by painful electrical stimulation

This study evaluated the effects of two different types of segmental/extra-segmental conditioning stimuli (tonic muscle pain and non-painful vibration) on the subjective experience (perceived pain intensity) and on the cortical evoked potentials to standardized test stimuli (cutaneous electrical stimuli). Twelve subjects participated in two separate sessions to investigate the effects of tonic muscle pain or cutaneous vibration on experimental test stimuli. The experimental protocol contained a baseline registration (test stimuli only), a registration with the test stimuli in combination with the conditioning stimuli, followed by a registration with the test stimuli only. In addition, the effects of the conditioning stimuli were examined at two anatomically separated locations (segmental and extra-segmental). Compared with the test stimulus alone, the perceived pain intensity and peak-to-peak amplitudes of the evoked potentials were unchanged in the presence of non-painful conditioning stimuli at either location. In contrast, a significant decrease of the perceived pain intensity and peak-to-peak amplitudes was found in the presence of painful conditioning stimuli at the extra-segmental sites. Moreover, the topographic maps of the 32-channel recordings suggested that the distribution of the scalp evoked potentials was almost symmetrical around the vertex Cz in the baseline registration. The evoked potentials were generally decreased during hypertonic saline infusion at the extra-segmental sites, but the distribution of the topographic maps did not appear to change. Vibration has previously been shown to inhibit pain, but in the present study the perceived intensity of phasic painful electrical stimuli was unchanged. The reduced perceived pain intensity and the smaller peak-to-peak amplitude of the evoked potential in the presence of extra-segmental conditioning pain are in accordance with the concept of diffuse noxious inhibitory control.     

Effects of different ions on resting polarization and on the mass receptor potential of carotid body chemosensors

The carotid body and its own nerve were removed from cats anesthetized with sodium pentobarbital and placed in an air gap system; the carotid body was bathed in modified Locke's solution equilibrated with 50% O₂ in N₂, pH 7.43 at 35°C. The sensory discharges, changes in “resting” receptor polarization and the mass receptor potential evoked by ACh or NaCN were recorded with nonpolarizable electrodes placed across the gap. Receptor potentials and sensory discharges evoked by ACh showed an appreciable increase in amplitude and frequency when the preparation was bathed in eserinized Locke. Eserine did not change appreciably the responses evoked by NaCN. Excessive depolarization elicited by either ACh or NaCN was accompanied by sensory discharge block. Removal of K⁺ ions from the bathing solution induced receptor hyperpolarization and an increase in the amplitude of the evoked receptor potentials. An increase of K⁺ concentration had the opposite effect. Reduction of Na⁺ or NaCl to one half, or total removal of this salt, induced an initial reduction and later disappearance of the sensory discharges, some receptor hyperpolarization and a reduction in the amplitude of the evoked receptor potentials. Reduction or removal of Ca⁺⁺ produced receptor depolarization, a marked depression of the evoked receptor potentials, an increase in the frequency of the sensory discharges and a reduction in the amplitude of the nerve action potentials. High Ca⁺⁺ or Mg⁺⁺ had little or no effect on action potential amplitude or resting polarization, but decreased sensory discharge frequency and the evoked receptor potentials. Total or partial replacement of Ca⁺⁺ with Mg⁺⁺ induced complex effects: (1) receptor depolarization which occurred in low Ca⁺⁺, was prevented by addition of Mg⁺⁺ ions; (2) the amplitude of the evoked receptor potentials was depressed; (3) the nerve discharge frequency was reduced as it was in high Mg⁺⁺ solutions; and (4) the amplitude of the nerve action potentials was reduced as it was in low Ca⁺⁺ solutions. Temperature had a marked effect on the chemoreceptors since a t high temperatures the receptors were depolarized and the discharge frequency increased. The baseline discharge and responses evoked by ACh or NaCN were depressed at low temperatures. The results are discussed in terms of possible receptor mechanisms influenced by the different ions.     

On the ionic mechanism underlying adrenergic-cholinergic antagonism in ventricular muscle

In atrial muscle, acetylcholine (ACh) decreases the slow inward current (Isi) and increases the time-independent outward K+ current. However, in ventricular muscle, ACh produces a marked negative inotropic effect only in the presence of positive inotropic agents that elevate cyclic adenosine monophosphate (AMP). A two-microelectrode voltage-clamp method was used on cultured reaggregates of cells from 16--20-d-old embryonic chick ventricles to determine the effects of ACh on Isi and outward current during beta-adrenergic stimulation. Only double penetrations displaying low-resistance coupling were voltage-clamped. Cultured reaggregates are advantageous because their small size (50-- 250 microns) permits better control of membrane potential and adequate space clamp. Tetrodotoxin (10(-6) M) and a holding potential of --50 to --40 mV were used to eliminate the fast Na+ current. Depolarizing voltage steps above --40 mV caused a slow inward current to flow that was sensitive to changes in [Ca]o and was depressed by verapamil (10(- 6) M). Maximal Isi was obtained at --10 mV and the reversal potential was about +25 mV. Isoproterenol (10(-6) M) increased Isi at all clamp potentials. Subsequent addition of ACh (10(-6) M) rapidly reduced Isi to control values (before isoproterenol) without a significant effect on the net outward current measured at 300 ms. The effects of ACh were reversed by muscarinic blockade with atropine (5 X 10(-6) M). We conclude that the anti-adrenergic effects of ACh in ventricular muscle are mediated by a reduction in Ca2+ influx during excitation.     

Microdialysis measures of functional increases in ACh release in the hippocampus with and without inclusion of acetylcholinesterase inhibitors in the perfusate

Because brain extracellular acetylcholine (ACh) levels are near detection limits in microdialysis samples, an acetylcholinesterase (AChE) inhibitor such as neostigmine is often added to microdialysis perfusates to increase ACh levels in the dialysate, a practice that raises concerns that the inhibitor might alter the results. Two experiments compared functional differences in ACh release with and without neostigmine. In the first experiment, 30-60% increases in extracellular ACh concentrations in the hippocampus were evident during food-rewarded T-maze training with 20-500 nm neostigmine in the perfusate but no increases were seen without neostigmine. In the second experiment, 78% increases in ACh release in the hippocampus were seen after injections of the GABA(A) receptor antagonist, bicuculline, into medial septum only if neostigmine (50 nm) was included in the perfusate. These findings suggest that, in the hippocampus, endogenous brain AChEs are very efficient at removing extracellular ACh, obscuring differences in ACh release in these experiments. Therefore, inclusion of AChE inhibitors in the microdialysis perfusate may be necessary under some conditions for observations of functional changes in release of ACh in the hippocampus.     

Changes in the effect of acetylcholine on septo-hippocampal reactions after serotonin administration to rabbits

Impulse activity and focal evoked potentials appearing in the hippocampus in response to testing stimuli applied to the septum medial nucleus were recorded in nonimmobilized and unanaesthetized rabbits. The efficiency of acetylcholine (ACh) action on septo-hippocampal reactions was tested before and after microiontophoretic administration of the serotonin (5-OT) or stimulation of the raphe nuclei. The 5-OT and raphe stimulation produced significant changes in the ACh action on septo-hippocampal reactions. In most cases, after microiontophoretic administration of 5-OT, the efficiency of ACh diminished, independently of excitatory or inhibitory effect of the 5-OT. Thus, the modulating action of 5-OT consists not only in protracted trace changes of the magnitude of septo-hippocampal reactions but also in trace reduction of septo-hippocampal responses to ACh.     

The effect of selective attention on pattern-specific visual evoked potentials

In a complex choice reaction time experiment, patterned stimuli without luminance change were presented, and pattern-specific visual evoked potentials to lower half-field stimulation were recorded. Two experimental conditions were used. The first was the between-field selection, where square patterns were presented in either the lower or the upper half of the visual field. In a given stimulus run one of the half-fields was task-relevant, and the subjects' task was to press a microswitch to stimuli of higher duration value (GO stimuli), while they had to ignore shorter ones, i. e. stimuli of lower apparent spatial contrast (NOGO stimuli). They had to ignore the stimuli appearing in the irrelevant half-field (IRR stimuli). In order to ensure proper fixation, the subjects had to press another microswitch at the onset of a dim light at the fixation point (CRT stimuli). Our second experimental condition was the within-field selection, where the GO, NOGO, and IRR stimuli appeared in the lower half of the visual field. GO and NOGO were square patterns while IRR stimuli were constructed of circles, or vice versa. (The CRT stimuli were the same as in the previous condition.) Three pattern-specific visual evoked potential components were identified, i. e. CI (70 ms latency), CII (100 ms latency), and CIII (170 ms latency). There were marked selective attention effects on both the CI-CII and CII-CIII peak-to-peak amplitudes. In both experimental conditions, responses with the highest amplitude were evoked by the GO type of stimuli, while the IRR stimuli evoked the smallest responses. According to these results, attention effects on the pattern-specific visual evoked potentials in the first 200 ms cannot be attributed to a simple stimulus set kind of selection.     

Suppression of F-VEP during isoflurane-induced EEG suppression

We recorded visual evoked potentials (VEPs) to flash stimuli in moderately deep anaesthesia when EEG showed burst suppression pattern. Flash VEPs could consistently be recorded in all 8 test subjects during bursts but not during suppressions. We conclude that during isoflurane-induced EEG suppression VEPs to flash stimuli are also suppressed. This effect should be taken into account in evoked potential testing during anaesthesia.     

Cholinergic transmission at mechanosensory afferents in the crayfish terminal abdominal ganglion

Electrical stimulation of mechanosensory afferents innervating hairs on the surface of the exopodite in crayfish Procambarus clarkii (Girard) elicited reciprocal activation of the antagonistic set of uropod motor neurones. The closer motor neurones were excited while the opener motor neurones were inhibited. This reciprocal pattern of activity in the uropod motor neurones was also produced by bath application of acetylcholine (ACh) and the cholinergic agonist, carbamylcholine (carbachol). The closing pattern of activity in the uropod motor neurones produced by sensory stimulation was completely eliminated by bath application of the ACh blocker, d-tubocurarine, though the spontaneous activity of the motor neurones was not affected significantly. Bath application of the acetylcholinesterase inhibitor, neostigmine, increased the amplitude and extended the time course of excitatory postsynaptic potentials (EPSPs) of ascending interneurones elicited by sensory stimulation. These results strongly suggest that synaptic transmission from mechanosensory afferents innervating hairs on the surface of the tailfan is cholinergic.Bath application of the cholinergic antagonists, dtubocurarine (vertebrate nicotinic antagonist) and atropine (muscarinic antagonist) reversibly reduced the amplitude of EPSPs in many identified ascending and spiking local interneurones during sensory stimulation. Bath application of the cholinergic agonists, nicotine (nicotinic agonist) and oxotremorine (muscarinic agonist) also reduced EPSP amplitude. Nicotine caused a rapid depolarization of membrane potential with, in some cases, spikes in the interneurones. In the presence of nicotine, interneurones showed almost no response to the sensory stimulation, probably owing to desensitization of postsynaptic receptors. On the other hand, no remarkable changes in membrane potential of interneurones were observed after oxotremorine application. These results suggest that ACh released from the mechanosensory afferents depolarizes interneurones by acting on receptors similar to vertebrate nicotinic receptors.Abbreviations ACh cetylcholine - mns motor neurones - asc int ascending interneurone     

The frog interosseal muscle fiber as a new model for patch clamp studies of chemosensitive- and voltage-sensitive ion channels: actions of acetylcholine and batrachotoxin

The patch clamp technique was used to record the currents flowing through single ion channels in isolated frog muscle fibers. The majority of the acetylcholine (ACh)-activated channels had a conductance of 32 pS, although 20 pS channels were also occasionally observed. Lifetimes of ACh-activated channels increased with the transmembrane potential in the range from - 30 mV to - 105 mV. In these same fibers we also observed channels which were activated by low concentrations of batrachotoxin (BTX; 10 nM). These channels, presumed to be Na channels, had a conductance of 19 pS and opened at potentials at which Na channels would not normally open. A notable feature of these BTX-activated channels was that they opened and closed repeatedly. Therefore, it appears that the toxin, in addition to activating Na channels, also blocks the inactivation process. The physiological properties of these channels reveal significant differences between the ion channels of tissue-cultured and mature tissues.     

Changes in the Parameters of Quantal Acetylcholine Release after Activation of PAR1-Type Thrombin Receptors at the Mouse Neuromuscular Junctions

In mature and newly formed neuromuscular synapses of mouse skeletal muscles, miniature endplate potentials (MEPPs) and multiquantal endplate potentials (EPPs) evoked by a single stimulation of the nerve were recorded using intracellular microelectrode technique. The mechanisms underlying the changes in spontaneous and evoked acetylcholine (ACh) release caused by the activation of PAR1-type muscle receptors induced by their peptide agonist TRAP6-NH₂ were studied. It has been shown for the first time that, in either mature or newly formed motor synapses, the activation of PAR1 that lack presynaptic localization causes a sustained increase in the MEPP amplitude due to the increase in the ACh quantal size at the presynaptic level. It was found that phospholipase C (PLC) participates in the signaling mechanism triggered by the PAR1 activation. Exogenously applied brain-derived neurotrophic factor (BDNF) mimics the effect of activation of PAR1 by TRAP6-NH₂. Moreover, an increase in the MEPP amplitude caused by the peptide PAR1 agonist was fully prevented by blocking the BDNF receptors–tropomyosin receptor kinases B (TrkB). Thus, it has been shown for the first time that the increase in ACh quantal size due to the activation of PAR1 in motor synapses is mediated by a complex signaling cascade that starts at the postsynaptic level of the motor synapse and ends at the presynaptic level. It is expected that the activation of PAR1 at the muscle fiber membrane followed by the PLC upregulation results in the release of neurotrophin BDNF as a retrograde signal. Its effect on the presynaptic TrkB receptors triggers the cascade leading to an increase in the quantal size of ACh.     

Pharmacological identification of acetylcholine receptor subtypes in echinoderm smooth muscle (Sclerodactyla briareus)

Contractions of an echinoderm (sp. Sclerodactyla briareus) smooth muscle, the longitudinal muscle of the body wall (LMBW), were evoked by acetylcholine (ACh) and agonists: epibatidine, muscarine and nicotine (in order of force generation: ACh>muscarine=epibatidine>nicotine). ACh-induced contractions were blocked by atropine by 50%, and methoctramine, by 30%. ACh responses were also blocked by 25% by methyllycaconitine (MLA) but not by d-tubocurarine (dTC). Muscarine initiated large contractions that were completely blocked by atropine. To elucidate possible muscarinic ACh receptor (mAChR) subtypes, muscarinic agonists (oxotremorine, pilocarpine) and antagonists (methoctramine, pirenzepine) were tested. Oxotremorine, pilocarpine, and pirenzepine each enhanced resting tonus and potentiated ACh-induced contractions (order of potency: pilocarpine>oxotremorine=pirenzepine). Muscarine, oxotremorine or pirenzepine generated phasic, rhythmic contractions. Nicotine-induced contractions were almost completely blocked by dTC but were not altered by atropine. Large contractions evoked by epibatidine were potentiated by dTC whereas atropine had no effect on them. MLA blocked spontaneous rhythmicity. Cholinesterase inhibitors, neostigmine or physostigmine, caused marked potentiation of ACh-induced contractions and initiated rhythmic slow wave contractions in previously quiescent muscles. The present pharmacological evidence points to the co-existence of excitatory nicotinic ACh receptor (nAChRs) and mAChRs where nAChRs possibly modulate tone, and the mAChRs initiate and enhance rhythmicity.     

Inhibitory synaptic potentials of the smooth muscle cells of guinea pig taenia coli

A single submaximal intramural application of rectangular stimuli (duration 0.2–0.5 msec) to an atropine-treated taenia coli muscle band evoked inhibitory postsynaptic potentials (IPSP) and a marked relaxation of the muscle band in the vast majority of muscle cells. The latency period of the IPSP was 122±16 msec; the times for a rise and fall of amplitude were 96±8 and 370±60 msec, respectively. The mean latency period of muscle relaxation was 800 msec. The latency period, and especially the amplitude of the IPSP depended on the intensity of the intramural stimulation. This indicates that one muscle cell is inhibited by several nerve fibers. IPSP evoked by threshold stimuli displayed a tendency toward summation, while the amplitude of the second and of subsequent IPSP evoked by low-frequency maximal stimuli was always less than that of the first IPSP. After periodic stimulation (frequency 10–60 impulses/min) was discontinued, a posttetanic decrease in IPSP amplitude was observed. Anodic polarization of the muscle band with a direct current raised the effectiveness of synaptic transmission, as was evidenced by the considerable increase in IPSP amplitude. When the muscle membrane was hyperpolarized with noradrenaline, IPSP inhibition was reversible. This is evidence that the unknown mediator and noradrenaline have a common ionic inhibitory mechanism.A. A. Bogomol'ts Institute of Physiology of the Academy of Sciences of the Ukrainian SSR, Kiev. Translated from Neirofiziologiya, Vol. 2, No. 5, pp. 544–551, September–October, 1970.     

Alteration of Acetylcholine Penetration into, and Effects on, Venom-Treated Squid Axons by Physostigmine and Related Compounds

Choline and neostigmine markedly antagonize the effect of acetylcholine (ACh) on the action potential of the venom-treated squid axon, although they themselves have no effect on conduction. Physostigmine also antagonizes the blocking action of ACh at a concentration well below that which has any effect on conduction. In contrast, d-tubocurarine (curare) increases the effect of ACh on the action potential. Choline, neostigmine, and physostigmine markedly decrease the penetration of C¹⁴-labeled ACh into the axoplasm of the squid axon. Curare, in contrast, increases the penetration of ACh, whereas dimethylcurare gives variable results. The results provide an explanation why physostigmine and neostigmine do not influence the action of ACh on axonal conduction in a way similar to that observed at the junction. The additive effect of curare and ACh on the action potential may be due either to the greater rate of penetration of ACh or to an additive effect of the two compounds on the receptor, or to a combination of both factors.     

Ultrastructure and electrical properties of the hyperneural muscle of Periplaneta americana

The hyperneural muscle of Periplaneta americana is striated with an A-band at least 2 μm long. Z-bands were discrete units, but arranged with some order in the myoplasm. The sarcoplasmic reticulum was reduced and 1 thick was surrounded by 10 to 12 thin myofilaments. The muscle is innervated from the median nerves by axons containing electron-dense granules which may be opaque near the neuromuscular junction amid numerous synaptic vesicles. Depolarizing intracellular current injection produces an ohmic voltage response of the membrane potential and neurally evoked contraction is effected by summated excitatory postsynaptic potentials. All contractal activity ceases when the innervation is removed. The muscle appears to be electrically inexcitable and to be under obligatory control of central motor units. By virtue of attachments along the ventral nerve cord in the abdomen, the hyperneural muscle, when activated, moves the nerve cord unidirectionally. In effect, the hyperneural muscle is called upon by the central nervous system to move the ventral nerve cord presumably into a greater mix with the haemolymph in response to as yet unknown stimuli.