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Biomedical subjects

R Gruener

Publications and source records attributed to R Gruener.

At least 37 records · Page 2Linked to original sources

Halothane shortens acetylcholine receptor channel kinetics without affecting conductance.

The extracellular patch-clamp technique was used to examine how halothane, a general anesthetic, affects the properties of single nicotinic acetylcholine receptor channels of embryonic Xenopus skeletal muscle cells grown in culture. Under control conditions, single-channel events showed a bimodal distribution on the basis of current amplitudes. This distribution was maintained during exposure to halothane and its washout. In addition, the mean current value of the low-and high-amplitude channels was unaffected by the presence of the anesthetic at clinically relevant concentrations. In contrast, halothane shortened the burst durations of both channel types in a concentration-dependent manner. This shortening of burst durations may be an expression of the more rapid relaxation of the channel protein to the nonconducting state, possibly due to the disordering effect of the anesthetic on membrane lipids in which the receptor protein is embedded. This functional change, in the behavior of the synaptic receptor, provides further direct information on the mode of action of general anesthetics.

Animals↗

Association of post-anaesthetic hyperthermia with abnormal muscle characteristics: a case report.

A previously healthy 18-year-old male, following appendectomy developed post-anaesthetic hyperthermia (42.1 degrees C) with an elevation of serum creatine kinase and activated partial thromboplastin time. Repeated arterial blood gases were normal. Cooling and anti-pyretic medication did not control the fever. In contrast, sodium dantrolene appeared effective in lowering the patient's temperature and normalizing the vital signs, both acutely and over the following three days. Subsequent muscle biopsy revealed a normal contracture response to caffeine alone or in the presence of halothane. However, the muscle had a larger than normal potentiation of evoked twitch tension in the presence of caffeine and halothane. Electrophoresis of the muscle revealed a marked increase of an unidentified low molecular weight protein. The patient's clinical course, and the results of the muscle studies, suggest that an abnormality of skeletal muscle.

Adolescent↗

Calcium uptake by isolated sarcoplasmic reticulum: examination of halothane inhibition, pH dependence, and Ca2+ dependence of normal and malignant hyperthermic human muscle.

Ca2+ uptake and release in muscle homogenates and fragmented sarcoplasmic reticulum were examined in biopsy specimens from nonsusceptible and malignant hyperthermia (MH) susceptible patients. Ca2+ flux was examined by the filter binding assay technique using 45Ca. It was found that Ca2+ uptake and release were the same in both normal and MH muscle homogenates. Halothane inhibited the uptake of Ca2+ by the sarcoplasmic reticulum. The halothane inhibition of Ca2+ uptake in normal and MH sarcoplasmic reticulum was fitted to a single line with a correlation coefficient (r) of -0.958. The pH and Ca2+ dependence of Ca2+ uptake were the same for both normal and MH sarcoplasmic reticulum. The pK for Ca2+ uptake is approximately 5.9. It is concluded that the Ca2+ uptake function of the muscle from the five patients with MH examined is not abnormal and might not be the locus for the initiation of MH.

Calcium↗

Conduction velocities in single fibers of diseased human muscle.

Focal sarcolemmal lesions, segmental degeneration, and fiber splitting are observed in Duchenne muscular dystrophy and have been proposed to be major contributory causes of dysfunction of this disease. The presence of these abnormalities should affect impulse conduction along the sarcolemma. To test this prediction, we measured conduction velocities of the action potential in normal and diseased human intercostal muscle fibers by means of intracellular microelectrodes. The resting potentials of fibers from patients with Duchenne dystrophy, Becker dystrophy, and motor neuron disease were partially depolarized, and conduction velocities in these fibers were slower than normal. When the membrane potential was artifically hyperpolarized, the conduction velocity in Becker dystrophy fibers was not significantly different from normal. However, conduction velocity values in Duchenne dystrophy or motor neuron disease fibers were significantly lower than normal regardless of the level of membrane hyperpolarization. These data are analyzed in light of the presence of morphologic lesions in the diseased muscle fibers.

Action Potentials↗

Interpretation of light scattering associated with prolonged neural activity and temperature changes.

Changes in light scattering from lobster giant axon which accompany the action potential were observed during periods of prolonged stimulation and as a function of temperature. At an initial temperature of 10 degrees C most (more than 90%) axons produced positive light scattering signals which increased in amplitude when the temperature was lowered. At 2 and 5 degrees C approximately half of the axons produced positive scattering signals. The remaining half produced negative scattering signals which became positive when the temperature was raised to 10 degrees C. The amplitude of the negative signals followed sigmoid transition to positive values as a function of time. The time and temperature dependence of the signal are interpreted in terms of differential changes between the indices of refraction of the membrane matrix and the open or closed early activation channel.

Action Potentials↗

Light scattering and excitation in lobster giant axon. Effects of ion substitution.

Changes in the light scattering signal from single giant axons of lobster were observed during the propagation of the action potential in order to correlate membrane excitability with possible structural changes reflected in the optical properties of the axolemma. Substitution of guanidine and aminoguanidine for sodium resulted in a decreased action potential amplitude to 69 and 50% of control values, respectively. The amplitude of the light signal was, however, not significantly changed by these substitutions and is, therefore, reported to be independent of the transmembrane potential and current. The venom of the scorpion Leiurus quinquestriatus caused a marked prolongation of the action potential and the light scattering signal without significantly altering their amplitudes. A two-state model of the early (sodium) activation channel is suggested, in which the light scattering signal is correlated with a possible difference in the scattering efficiency between the states of the channel.

Action Potentials↗

Muscle insensitivity to tetrodotoxin: induction by alpha-bungarotoxin and removal by submechanical threshold stimulation.

Intramuscular injection of alpha-bungarotoxin (alphaBGT) into rat extensor digitorum longus muscles produced pharmacological blockade of neuromuscular transmission and resulted in denervation-like changes (Berg, D. and Hall, Z. (1975), J. Physiol. (London) 244:659-676). More than 80% of fibers from alphaBGT-injected muscles produced action potentials (ap's) in the presence of tetrodotoxin (TTX, 1 X 10(-6) M). Chronic electrical stimulation of these muscles, below the level necessary to elicit a contraction, resulted in a marked return toward normal of sarcolemmal sensitivity to TTX. After 4 days of submechanical threshold stimulation, less than 45% of alphaBGT-injected fibers produced ap's in the presence of TTX, whereas more than 80% of unstimulated fibers from contralateral control muscles exhibited resistance to TTX. These findings indicate that in addition to sarcolemmal sensitivity to acetylcholine, sensitivity of the sodium conductance mechanism to TTX is also directly influenced by muscle activity independent of contraction.

Animals↗

Hyperthyroid myopathy. Intracellular electrophysiological measurements in biopsied human intercostal muscle.

Morphological and electrophysiological studies were performed on intercostal muscle biopsies from 2 thyrotoxic patients. The diseased fibers had numerous areas of subsarcolemmal glyogen accumulations and abnormal membranous projections. Both Type I and Type II muscle fibers were atrophied. Diseased fibers were substantially depolarized and when artifically hyperpolarized showed earlier inactivation of the sodium conductance as a function of membrane potential, and a critical depolarization potential more depolarized than in normal fibers. When stimulated at 20 pulses/sec, or faster, the diseased fibers could not generate normal action potentials due to membrane depolarization and the appearance of a marked after-hyperpolarization. Muscle weakness associated with hyperthyroidism is attributed to the reduced membrane excitability.

Adult↗

Excitability modulation by taurine. Transmembrane measurements of neuromuscular transmission.

The presence of taurine, a non-essential amino acid, in nerve and muscle has been previously associated with inhibition of activity in the central nervous system, with the etiology of epileptogenic foci, and with the muscle weakness of muscular dystrophy. We present here data showing a small and probably insignificant effect of taurine on neuromuscular transmission per se, but significant hyperpolarization of the membrane potential in both taurine-incubated and taurine-loaded muscles. In addition, we found that taurine reduces the time course of the muscle action potential. The results are interpreted in terms of neuromuscular transmission and excitation-contraction coupling consequent to these phenomena. This interpretation is compatable with the hypothesis that taurine is involved in the genesis of muscular dystrophy where the membrane potential is depolarized. Our results and interpretation can also explain the anti-arrhythmic action of taurine on cardiac muscle.

Action Potentials↗

Intercostal muscle biopsy in human neuromuscular disease. Histochemical and electron microscopic studies.

External intercostal muscle biopsies were examined histochemically and by electron microscopy. The use of this muscle allowed correlation with physiological and pharmacological studies on the same specimens. Changes observed in musclar dystrophy and motor neurone disease resembled those previously described in biopsied limb muscle and underline the particular usefulness of this preparation in the study of human neuromuscular disease.

Adenosine Triphosphatases↗