The Mechanism of Acute Neuromuscular Weakness Induced by Chloroquine

1972 ◽  
Vol 50 (11) ◽  
pp. 1099-1103 ◽  
Author(s):  
G. A. Vartanian ◽  
H. M. Chinyanga
Keyword(s):  
Clinical Practice ◽  
Muscle Weakness ◽  
Muscle Fiber ◽  
Mechanism Of Action ◽  
Action Potentials ◽  
Nerve Fibers ◽  
End Plate ◽  
Excitable Membranes ◽  
Single Nerve ◽  
Electrically Excitable Membranes

Chloroquine caused muscle weakness in neuromuscular preparations of both frog and cat in doses as low as those used in clinical practice. Studies of end-plate and action potentials in the muscle fibers and action potentials in single nerve fibers showed that the muscle weakness induced by chloroquine resulted from depression of the excitability of the electrically excitable membranes of the axon and muscle fiber. This led to the decrease of action potentials of the axon resulting in the reduction of transmitter output at the end plate and decreased firing index, as well as to the decrease in the amplitude of action potential of the muscle fiber itself. It was inferred that the mechanism of action of chloroquine was similar to that of local anesthetics.

An intracellular study of chemosensory fibers and endings

1980 ◽  
Vol 44 (6) ◽  
pp. 1077-1088 ◽  
Author(s):  
Y. Hayashida ◽  
H. Koyano ◽  
C. Eyzaguirre
Keyword(s):  
Carotid Body ◽  
Action Potentials ◽  
Physiological Saline ◽  
Mean Amplitude ◽  
Nerve Fibers ◽  
Chemical Stimulation ◽  
Nerve Terminals ◽  
Generator Potential ◽  
Single Nerve ◽  
Frequency Changes

1. The carotid body and its nerve, removed from anesthetized cats, were placed in physiological saline flowing under paraffin oil. The nerve, lifted into the oil, was used for either electrical stimulation or recording of the total afferent discharge. Intracellular recordings were obtained from individual nerve fibers and endings within the carotid body. The recording sites were identified by injecting Procion yellow through the intracellular electrodes; the tissues were then prepared for histology and observed with episcopic fluorescence or Nomarski optics. 2. Intracellularly recorded chemosensory fibers conducted at 1.1-30 m/s and usually displayed action potentials of regular amplitude. At times, however, some spikes become partially blocked while others maintained their original amplitude. "Natural" (hypoxia) or chemical (ACh or NaCN) stimulation induced different patterns of frequency changes of the large and small action potentials. This indicated nerve fiber branching at some distance from the recording site. 3. Intra- and extracellularly recorded spikes were blocked in 0 [Na+]0 by tetrodotoxin (TTX) or procaine. 4. During chemical stimulation, a slowly occurring depolarization (receptor or generator potential) was recorded intracellularly from the afferent fibers. It developed concomitantly with the increase in discharge. 5. Impalement of single nerve terminals (histologically identified) showed numerous "spontaneous" depolarizing potentials (SDPs) that had a mean amplitude of 5.6 mV, a mean duration of 46.1 ms, and nearly random distribution. They increased in frequency and summated during chemical stimulation. SDPs originated from either the site of recording or from neighboring areas. When the SDPs attained a certain amplitude, they seemed to give rise to action potentials. Also, relatively well developed or partially blocked spikes (apparently originating elsewhere) were recorded from single nerve terminals. 6. The receptor (generator) potential of chemosensory receptors appears to be an integrated response formed by multiple activity originating in different nerve endings.

scholarly journals CHARACTERIZATION OF A UNIQUE MUSCLE CELL LINE

1974 ◽  
Vol 61 (2) ◽  
pp. 398-413 ◽  
Author(s):  
David Schubert ◽  
A. John Harris ◽  
Carrick E. Devine ◽  
Stephen Heinemann
Keyword(s):  
Smooth Muscle ◽  
Cell Line ◽  
Action Potentials ◽  
Creatine Phosphokinase ◽  
Clonal Cell Line ◽  
Excitable Membranes ◽  
Hyperpolarizing Response ◽  
Electrically Excitable Membranes

A clonal cell line derived from a mouse neoplasm is described which shares many properties with smooth muscle. The cells have electrically excitable membranes capable of generating overshooting action potentials, and they contract both spontaneously and with electrical stimulation. They respond to the iontophoretic application of acetylcholine with a depolarizing response, and to norepinephrine with a hyperpolarizing response. Electron microscopy reveals that the cells have a morphology similar in many, but not all, respects to that of smooth muscle cells in vivo. The cells secrete soluble collagen-like molecules in addition to several proteins of undefined function. Finally, there is an increase in the specific activities of creatine phosphokinase and myokinase associated with increased cell density and the cessation of cell division.

Phase portraits of dystrophic and nondystrophic mouse muscle-fiber action potentials

1965 ◽  
Vol 208 (4) ◽  
pp. 724-731 ◽  
Author(s):  
Titus C. Evans ◽  
Byron A. Schottelius
Keyword(s):  
Muscle Fiber ◽  
Action Potentials ◽  
Sodium Ion ◽  
Phase Portraits ◽  
Dystrophic Muscle ◽  
General Increase ◽  
Ion Conductance ◽  
Mouse Muscle ◽  
Intracellular Action ◽  
Fiber Action

Intracellular action potentials from normal, control nondystrophic and dystrophic mouse soleus muscle fibers were recorded in both voltage-time and phase-portrait plots. Flattening of a normally curved portion in certain dystrophic muscle-fiber phase portraits suggested a greater than usual secondary entry of sodium ions after the peak of the action potential. Low-chloride studies excluded an abnormal chloride current as the cause of the flattening. It appears that inactivation of sodium ion conductance may be delayed or reduced, or both, in certain fibers of mice with hereditary muscular dystrophy. This is consistent with a general increase in membrane permeability. No definite negative afterpotential was noted in most mouse muscle-fiber action potentials.

The biphasic morphology of voluntary and spontaneous single muscle fiber action potentials

1994 ◽  
Vol 17 (11) ◽  
pp. 1301-1307 ◽  
Author(s):  
Daniel Dumitru ◽  
John C. King ◽  
William van der Rijt ◽  
Dick F. Stegeman
Keyword(s):  
Muscle Fiber ◽  
Action Potentials ◽  
Single Muscle ◽  
Single Muscle Fiber ◽  
Fiber Action

Influence of presynaptic receptors on neuromuscular transmission in rat

1982 ◽  
Vol 242 (5) ◽  
pp. C366-C372 ◽  
Author(s):  
D. F. Wilson
Keyword(s):  
Transmitter Release ◽  
Action Potentials ◽  
Physiological Function ◽  
Motor Nerve ◽  
Presynaptic Receptors ◽  
End Plate ◽  
Feedback Pathway ◽  
Partial Blockade ◽  
Ach Receptors

The presence and physiological significance of acetylcholine (ACh) receptors on motor nerve terminals was examined at the rat diaphragm neuromuscular junction. Intracellular recording techniques were used to monitor end-plate potentials (EPP), miniature end-plate potentials (MEPP), and resting potentials of the muscle fibers. Muscle action potentials were blocked by the cut-muscle technique. Quantal release was determined by the ratio EPP/MEPP, after correcting for nonlinear summation. Blockade of acetylcholinesterase with eserine and neostigmine was tested to determine the influence of residual ACh on transmitter release. Partial blockade of ACh receptors with curare was examined to further clarify the role of these presynaptic receptors. The experiments demonstrate that residual ACh inhibits transmitter release and that blockade of ACh receptors enhances transmitter release. It is concluded that presynaptic ACh receptors exist and that they serve an important physiological function. It is suggested that the presynaptic ACh receptors normally serve to limit transmitter release in a negative feedback pathway.

Electrical properties and innervation of fibers in the orbital layer of rat extraocular muscles

1989 ◽  
Vol 61 (1) ◽  
pp. 116-125 ◽  
Author(s):  
J. Jacoby ◽  
D. J. Chiarandini ◽  
E. Stefani
Keyword(s):  
Electrical Properties ◽  
Nerve Stimulation ◽  
Action Potentials ◽  
Time Course ◽  
Lucifer Yellow ◽  
Extraocular Muscles ◽  
Resting Potential ◽  
Inferior Rectus ◽  
End Plate ◽  
Orbital Layer

1. The inferior rectus muscle of rat, one of the extraocular muscles, contains two populations of multiply innervated fibers (MIFs): orbital MIFs, located in the orbital layer of the muscle and global MIFs, found in the global layer. The electrical properties and the responses to nerve stimulation of orbital MIFs were studied with single intracellular electrodes and compared with those of twitch fibers of the orbital layer, MIFs of the global layer, and tonic fibers of the frog. 2. About 90% of the orbital MIFs did not produce overshooting action potentials. In these fibers the characteristics and time course of the responses to nerve stimulation varied along the length of the fibers. Within 2 mm of the end-plate band of the muscle, the responses consisted of several small end-plate potentials (EPPs) and a nonovershooting spike. Distal to 2 mm, the responses in most fibers consisted of large and small EPPs with no spiking response. Some fibers produced very small spikes surmounted on large EPPs. 3. Overshooting action potentials were observed in approximately 10% of the orbital MIFs recorded between the end-plate band and 2 mm distal. The presence or absence of action potentials was not related to the magnitude of the resting potential of the fibers. 4. The threshold of nerve stimulated responses in orbital MIFs was the same as that in orbital twitch fibers. A large number of orbital MIFs had latencies equal to those for the orbital twitch fibers recorded at the same distance from the end-plate band, but the average latency was greater in the MIFs. The latency of orbital MIFs was about one-half of that for the MIFs of the global layer. The values for the effective resistance and membrane time constant of orbital MIFs fell between those for orbital twitch fibers on the one hand, and global MIFs and frog tonic fibers on the other. 5. In order to compare electrical properties with innervation patterns, fibers identified electrophysiologically as orbital MIFs were injected with the fluorescent dye Lucifer yellow and then traced in Epon-embedded, serial transverse sections. In addition to numerous superficial endings distributed along the fibers, a single "en plaque" ending was also found in the end-plate band that resembled the end plates of the adjacent orbital twitch fibers. 6. From these results we conclude that the electrical activity of orbital MIFs varies along the length of the fibers.(ABSTRACT TRUNCATED AT 400 WORDS)

A study of the effect of X-rays on the electrical properties of mammalian nerve and muscle

1963 ◽  
Vol 157 (969) ◽  
pp. 536-561 ◽  
Keyword(s):  
Dose Rate ◽  
Action Potentials ◽  
Time Course ◽  
Low Dose ◽  
High Dose ◽  
X Rays ◽  
Low Dose Rate ◽  
End Plate ◽  
Small Doses ◽  
Motor End Plate

Resting potentials, action potentials, and miniature end-plate potentials have been re­corded from isolated phrenic-diaphragm preparations of the rat during and after irradiation with X-rays. Relatively small doses of a few thousand roentgens have no obvious effect on the preparation for many hours but larger doses, of the order of 70 to 150 kr irreversibly block neuromuscular transmission. The block is not accompanied by any change in the size of action potentials, resting potentials, membrane constants or miniature potentials recorded in the muscle with intracellular electrodes, or in the size of action potentials recorded in the nerve. Records made at the motor end-plate show that the cause of the block is a ‘pre-synaptic ’ failure of impulse propagation in the intramuscular part of the nerve. The time course of the failure depends largely on the rate at which X-rays are delivered to the pre­paration: at a high dose-rate (70kr/min) the block develops rapidly and is accompanied by an increase in the frequency of miniature potentials; at a low dose-rate (7 kr/min) larger doses are required, the latency is longer and the miniature potentials continue at a normal frequency. The sequence in which different parts of the muscle become blocked, the abrupt nature of the failure at an individual motor end-plate, and the increase in frequency of the miniature potentials together suggest that the action of X-rays is to block conduction in the nerve near its terminals, possibly by depolarizing points where the axons branch and the safety factor for the propagation of impulses is low. The results reported in this paper do not support the hypotheses that small doses of X-rays at a high or a low dose-rate lead to an initial 'enhancement' of function or that they produce immediate and reversible changes in the permeability of excitable membranes to ions.

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