Laminins during muscle development and in muscular dystrophies

Cellular interactions with the extracellular matrix during muscle formation and in muscular dystrophy have received increased interest during the past years. Laminins constitute a growing family of proteins with complex expression patterns in forming basement membranes during muscle development. In skeletal muscle, laminins constitute major ligands for cell surface receptors involved in the transmission of force from the cell interior, but laminins might also influence signal transmission events during muscle formation and in muscle regeneration. During myogenesis the laminin alpha1 chain is present around the epithelial somite; but later, in forming muscle, the laminin alpha1 chain is restricted to the myotendinous junction. The laminin alpha2, alpha4 and alpha5 chains are major laminin chains in the muscle basement membrane during muscle formation, but laminin alpha4 and alpha5 chains are absent in adult muscle. The importance of laminins for muscle integrity is manifested in congenital muscular dystrophies with defects in the laminin alpha2 chain. There is no good evidence for the presence of laminin alpha1 chain in dystrophic muscle, but some other fetal muscle laminins can be detected in dystrophic muscle. Characterization of laminin expression patterns in muscular dystrophies might be of diagnostic and therapeutic value. In this paper, we review the recent publications on the biological functions of muscle laminins and discuss their roles in skeletal muscle.     

Microinjection of synthetic protein kinase inhibitor into single barnacle muscle fibers before and after cyclic AMP

Single muscle fibers from the barnacle Balanus nubilus have been used as a preparation to see if a synthetic 20-residue PKI (5-24)-peptide is able to block or reverse the stimulatory response of the ouabain-insensitive Na efflux to injected cAMP. The results obtained show that this peptide behaves as a powerful inhibitor of the cAMP-mediated response and is also able to partially reverse the sustained stimulation of the Na efflux observed in ouabain-poisoned fibers following the injection of subunit A of cholera toxin.     

Control of DNA integrity in skeletal muscle under physiological and pathological conditions

Skeletal muscle is a highly oxygen-consuming tissue that ensures body support and movement, as well as nutrient and temperature regulation. DNA damage induced by reactive oxygen species is present in muscles and tends to accumulate with age. Here, we present a summary of data obtained on DNA damage and its implication in muscle homeostasis, myogenic differentiation and neuromuscular disorders. Controlled and transient DNA damage appears to be essential for muscular homeostasis and differentiation while uncontrolled and chronic DNA damage negatively affects muscle health.     

Effects of the spinal cord section and of subsequent denervation on the mechanical properties of fast and slow muscles.

The Soleus muscle of the rat, 3--6 months old, becomes significantly faster than in the controls, if the spinal cord is cut at birth. Mechanical properties of Extensor Digitorum Longus (EDL) muscle are not altered by spinal cord section. In cordotomized animals Soleus muscle always remains slower than EDL muscle. Denervation, performed 3--6 months after birth, has the same slowing effects in the Soleus and EDL muscles, both in cordotomized and in the control animals.     

Effects of the spinal cord section and of subsequent denervation on the mechanical properties of fast and slow muscles

Summary The Soleus muscle of the rat, 3–6 months old, becomes significantly faster than in the controls, if the spinal cord is cut at birth. Mechanical properties of Extensor Digitorum Longus (EDL) muscle are not altered by spinal cord section. In cordotomized animals Soleus muscle always remains slower than EDL muscle. Denervation, performed 3–6 months after birth, has the same slowing effects in the Soleus and EDL muscles, both in cordotomized and in the control animals.     

Microinjection of synthetic protein kinase inhibitor into single barnacle muscle fibers before and after cyclic AMP

Summary Single muscle fibers from the barnacleBalanus nubilus have been used as a preparation to see if a synthetic 20-residue PKI (5-24)-peptide is able to block or reverse the stimulatory response of the ouabain-insensitive Na efflux to injected cAMP. The results obtained show that this peptide behaves as a powerful inhibitor of the cAMP-mediated response and is also able to partially reverse the sustained stimulation of the Na efflux observed in ouabain-poisoned fibers following the injection of subunit A of cholera toxin.Warmest thanks to Prof. E. H. Fischer and Kurt Diltz for a sample of sPK1. This work received support from NSF, the Graduate School Research Committee and from NIH through a General Research Support Grant to the University of Wisconsin Medical School.     

Leptin, but not a β3-adrenergic agonist, upregulates muscle uncoupling protein-3 messenger RNA expression: short-term thermogenic interactions

The short-term effects of leptin and a β₃-adrenoceptor agonist on thermogenesis and expression of uncoupling proteins (UCPs) in brown adipose tissue (BAT) and muscle and their possible interactions were assessed. One hour after administration of the β₃-adrenoceptor agonist Trecadrine, a statistically significant increase in UCP1 messenger RNA (mRNA) expression in BAT was observed, whereas UCP2 and UCP3 in both BAT and gastrocnemius muscle were unaffected. Leptin induced an upregulation of UCP3 mRNA in muscle, with no changes in BAT UCP1 mRNA. A statistical interaction was found between leptin and Trecadrine in rectal temperature. The present study provides evidence, for the first time, of the induction of UCP3 mRNA expression in skeletal muscle by leptin in nongenetically obese animals. Received 5 March 1999; received after revision 19 April 1999; accepted 21 April 1999     

Die Rolle von Glukose im Erholungsprozess des Muskels

Summary It is well known that after exhausting muscle work glucose (or saccharose) leads to quick recovery in man. Experiments on rats have shown that in adult animals 50% of all creatine is present as creatine-phosphate (CP). In old animals above 22 months, only about 25% is present as CP. Diets with a 50% glucose content lead in old animals, in rest, to 50% CP in the muscle. Also after exhausting work on glucose diet the restitution is so complete that about 50% CP is present. The main reservoir of energy for the restitution of muscle, ADP ATP, comes from the breakdown of CP. The problem may be discussed whether high glucose diet may be damaging insulin production by exhaustion.     

Comparative action of toxins isolated from the venom of the scorpion (Androctonus australis) and the tentacles of the sea anemone (Anemonia Sulcata) on an isolated frog neuromuscular preparation]

We have shown that, if Scorpion venom is acting a skeletal muscle indirectly by releasing Acetycholine and directly by inducing an increase in intracellular free calcium, the main action of toxin II isolated from Anemonia Sulcata tentacles is presynaptic.     

Die Wirkung von Aldosteron («Electrocortin») auf den Natrium-, Kalium- und Glykogen-Stoffwechsel des isolierten Muskels

Summary (1) The influence of Aldosterone (Electrocortin) was compared with that of 17-oxycorticosterone (compound F). The exchange of Na²⁴ and K⁴² with the electrolytes of muscle was studied, with or without the addition of glucose and insulin. The diaphragm of the rat inRinger's solution was used.(2) Aldosterone (1 mg%) decreases the permeability of the muscle for Na²⁴ and K⁴² if glucose and insulin are present, i.e. when glycogen is produced. Without glucose it increases Na²⁴ exchange.(3) 17-oxycorticosterone in ten times greater concentration (10 mg%) has similar, but somewhat less influence on the permeability.     

Ventral neural tube cells differentiate into hepatocytes in the chick embryo

A population of ventral neural tube cells has recently been shown to migrate out of the hind brain neural tube via the vagus nerve and contribute to the developing gastrointestinal tract. Since liver is also innervated by the vagus nerve, we sought to determine if these cells also migrate into the liver. Ventral neural tube cells in the caudal hindbrain of chick embryos were tagged with a replication-deficient retroviral vector containing the LacZ gene on embryonic day 2. Embryos were processed for detection of labeled cells on embryonic day 5 and 11. Labeled cells were seen in the liver on both days and identified as hepatocytes. Previously, it was believed that all hepatocytes develop from the gut endoderm. Results of the present study show an additional source for the formation of liver cells. Received 25 August 1998; received after revision 5 November 1998; accepted 5 November 1998     

Uptake and transport of exogenous peroxidase in the masticatory muscles of the cat. Localization of motor neurons]

In the present work, a topographical localization of masticatory muscle motoneurons was undertaken. Horseradish peroxydase injected in each muscle can be transported in the retrograde direction to the corresponding motoneurons cell bodies. Jaw-closing muscle motoneurons were identified in the dorsal part of the motor trigeminal nucleus whereas jaw-opening muscle motoneurons were observed in the ventro-medial region.     

The enteric neural receptor for 5-hydroxytryptamine

An enteric neural receptor for serotonin (5-HT) has been characterized. This receptor was assayed, using 3H-5-HT as a radioligand, by rapid filtration of isolated enteric membranes and by radioautography. In addition, intracellular recordings were made from ganglion cells of the myenteric plexus. High affinity, saturable, reversible, and specific binding of 3H-5-HT was demonstrated both to membranes of the dissected longitudinal muscle with adherent myenteric plexus and the mucosa-submucosa. Radioautographs showed these 3H-5-HT binding sites to be in myenteric ganglia and in a broad unresolved band at the mucosal-submucosal interface. Antagonists active at receptors for other neurotransmitters than 5-HT, at either of the two known types of CNS 5-HT receptor, and at 5-HT uptake sites on serotonergic neurons failed to inhibit binding of 3H-5-HT. The structural requirements of analogues for binding to the enteric 5-HT receptor matched the known pharmacology of M or neural 5-HT receptors. A novel 5-HT antagonist was found. This compound, N-acetyl-5-hydroxytryptophyl-5-hydroxytryptophan amide (5-HTP-DP), antagonized the action of 5-HT on type II/AH cells of the myenteric plexus but did not affect the release or actions of acetylcholine (nicotinic or muscarinic) or substance P. 5-HTP-DP was also an equally potent displacer of 3H-5-HT from its binding sites on enteric membranes. It is concluded that the sites responsible for specific binding of 3H-5-HT are enteric M or neural 5-HT receptors. These receptors differ from those now known to be present in the CNS.     

Shivering during sleep: Relationship between muscle blood flow and fiber type composition

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.     

Shivering during sleep: relationship between muscle blood flow and fiber type composition.

The present study considers in rabbit: i) the relationship between muscle blood flow (BF) increase and fiber-type composition during shivering; ii) the influence of the vigilance states (Quiet Wakefulness, QW; Synchronized Sleep, SS; Desynchronized Sleep, DS) on this relationship. The results show that muscle BF increase during shivering is proportional to the slow-twitch oxidative (SO) fiber component in QW and SS; in DS the proportionality is lost. This is in accordance with the disappearance of shivering, together with all thermoregulatory effector responses, in this sleep state. Another muscle circulation pattern occurring at low ambient temperature, the relationship between BF increase and muscle depth, also disappears in DS. This confirms that the integrative control of muscle circulation, like other integrative mechanisms, is impaired during DS.     

Triadin: a multi-protein family for which purpose?

Triadin is a protein first identified as a member of the muscle calcium release complex, involved in calcium release for muscle contraction. However, its precise function in this complex is still undefined. Recently, triadin has been shown to be a multi-protein family, with different distribution of the various splice variants within the sarcoplasmic reticulum, raising the possibility of multiple functions for this family of polypeptides. Such functions may include involvement in excitation-contraction coupling, in triad targeting, in structural function or in muscle differentiation. The putative role(s) of triadin(s) will be discussed here.Received 5 May 2004; received after revision 4 June 2004; accepted 7 June 2004     

Effect of nerve stimulation on rat skeletal muscle. A study of plasma membrane

Summary The gastrocnemius muscle of the rat showed no morphological, histometric or plasma membrane changes, after sciatic nerve stimulation with a 5 mA current for 30 to 60 min, 10 mA for 30 min and 15 mA for 5 min. However, 10 mA for 60 and 200 min gave rise to mitochondrial and plasma membrane abnormalities. These changes were absent after a rest period. The results indicated the sciatic nerve stimulation at 10 mA for 60 and 200 min caused reversible changes in the rat skeletal muscle mitochondria and plasma membrane.     

Effect of nerve stimulation on rat skeletal muscle. A study of plasma membrane

The gastrocnemius muscle of the rat showed no morphological, histometric or plasma membrane changes, after sciatic nerve stimulation with a 5mA current for 30 to 60 min, 10 mA for 30 min and 15 mA for 5 min. However, 10 mA for 60 and 200 min gave rise to mitochondrial and plasma membrane abnormalities. These changes were absent after a rest period. The results indicated that the sciatic nerve stimulation at 10 mA for 60 and 200 min caused reversible changes in the rat skeletal muscle mitochondria and plasma membrane.