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Cloning and characterization of novel snake venom proteins that block smooth muscle contraction.

In this study, we isolated a 25-kDa novel snake venom protein, designated ablomin, from the venom of the Japanese Mamushi snake (Agkistrodon blomhoffi). The amino-acid sequence of this protein was determined by peptide sequencing and cDNA cloning. The deduced sequence showed high similarity to helothermine from the Mexican beaded lizard (Heloderma horridum horridum), which blocks voltage-gated calcium and potassium channels, and ryanodine receptors. Ablomin blocked contraction of rat tail arterial smooth muscle elicited by high K+-induced depolarization in the 0.1-1 microm range, but did not block caffeine-stimulated contraction. Furthermore, we isolated three other proteins from snake venoms that are homologous to ablomin and cloned the corresponding cDNAs. Two of these homologous proteins, triflin and latisemin, also inhibited high K+-induced contraction of the artery. These results indicate that several snake venoms contain novel proteins with neurotoxin-like activity.

Agkistrodon↗

Continuum rheology of muscle contraction and its application to cardiac contractility.

A set of constitutive equations is proposed to describe the mechanics of contraction of skeletal and heart muscle. Fiber tension is assumed to depend on the degree of chemical activation, the stretch ratio, and the rate of stretching of the fibers. The time rate of change of activation is governed by a differential equation. The proposed constitutive equations are used to model the time courses of isotonic and isometric twitches during contraction and relaxation phases of the muscle response to stimulation. Various contractility indices of the left ventricle are considered next by using the proposed constitutive equations. The present analysis introduces a new interpretation of the index of contractility (dP/dt)/P used in cardiac literature. It is shown that this index may not be related at all to the maximum speed of shortening and that it may be dependent on both preload and afterload. The development of pressure during isovolumetric contraction of the left ventricle is shown to be governed by a differential equation describing the time rate of change of tension during isometric contraction of myocardium fibers.

Animals↗

Isometric muscle contraction in endocrine myopathies.

Isometric contraction of the adductor pollicis muscle of the thumb was evoked by stimulating the ulnar nerve in 20 normal adults and 58 patients with endocrine disorders. We evaluated mechanical latency, electromechanical latency, contraction time, half relaxation time, isometric twitch force, compound muscle action potential, nerve conduction velocity, and relative refractory period. Mechanical characteristics were altered in diseases of the pituitary, thyroid, and parathyroid glands. The close relationship between thyroid hormone and contractile properties discriminated between hypo- and hyperthyroidism.

Adrenal Gland Diseases↗

Foscarnet inhibits vascular smooth muscle contraction.

Foscarnet inhibited noradrenaline and calcium-mediated contractions of the isolated perfused tail artery of the rat. When the noradrenaline contractile response was split into two components, where the first was due to the release of calcium from intracellular stores and the second to the influx of calcium from the extracellular fluid, foscarnet (30 microM) inhibited only the first component of the response. Foscarnet did not inhibit the calcium influx component of the noradrenaline contraction, nor did it affect the inhibition of this component by the L-type calcium channel antagonists verapamil and nicardipine. These results indicate that foscarnet inhibits vascular smooth muscle contraction by inhibiting calcium release from intracellular stores.

Animals↗

Modulation of activity in starling cochlear ganglion units by middle-ear muscle contractions, perilymph movements and lagena stimuli.

In the present study three groups of cochlear ganglion neurons were detected which differed in respect to their tone-evoked and spontaneous activity: auditory units which showed an irregular spontaneous discharge, non-auditory neurones with regular activity and such with an irregular spontaneous discharge pattern. Electrically-elicited contractions of the middle-ear muscle influenced the tone-evoked and/or the spontaneous activity of the auditory and the non-auditory neurones with irregular spontaneous discharge but not, however, the regularly firing units. Similar results were obtained with imposed perilymph movements in the cochlea (evoked via the vestibular system. Fractions of all three groups of cochlear ganglion neurones were responsive to direct deformations of the membraneous lagena. Several (auditory and non-auditory) units with irregular discharge were excited during a basilar membrane displacement towards scala vestibuli whereas a basilar membrane motion towards scala tympani resulted in a decrease of the discharge rate. A few units showed a different reaction. The results provide evidence that the neurones with periodic spontaneous discharge innervate the lagena and that this sense organ has no auditory significance in birds. The peripheral origin of the 'non-auditory' neurones with irregular spontaneous activity remains undecided and might be the macula lagenae or the apical portion of the basilar papilla.

Action Potentials↗

Relieving effect of TENS on painful muscle contraction produced by an impairment of reciprocal innervation: an electrophysiological analysis.

A young female outpatient experienced painful tonic contractions in the right triceps surae muscles as a result of a partial damage of the right peroneal nerve. Electrophysiological recordings of the soleus muscle showed a tonic EMG activity and an hyperexcitability of the monosynaptic H reflex (Hmax/Mmax ratio: 90%). Application of transcutaneous electrical nerve stimulation (TENS, 1-2 min) on the peroneal nerve trunk at the head of the fibula resulted both in a pain relief and in the disappearance of the tonic activity in the muscles supplied by the antagonist nerve. Simultaneously, the Hmax/Mmax ratio decreased to normal values (49%). This was followed by an after-effect lasting more than 30 min. The potential role of an impairment of reciprocal inhibition in the originating mechanism of these troubles is discussed.

Adolescent↗