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R C Carlsen

Publications and source records attributed to R C Carlsen.

At least 19 recordsLinked to original sources
PubMed1992

Coordinated expression of phosphorylase kinase subunits in regenerating skeletal muscle.

The developmental expression of the alpha, beta, and gamma subunits of skeletal muscle phosphorylase kinase has been examined in regenerating muscle. Rat extensor digitorum longus (EDL) muscles, treated with bupivacaine, promptly undergo a rapid degeneration of the muscle, followed by regeneration and recovery of essentially normal morphology and physiology by 3-4 weeks post-treatment (Hall-Craggs, E. C. B., and Seyan, H. S. (1975) Exp. Neurol. 46, 345-354). Phosphorylase kinase activity dropped to approximately 10% of control within 3 days of bupivacaine treatment and remained at this low level for several days but had attained at least 60% of normal levels by day 21. The pH 6.8/8.2 activity ratio was unusually high during the period of low activity, suggesting that the catalytic activity was not under normal regulation at this time. The subunit mRNAs were readily detected in control EDL but were undetectable at day 3 post-bupivacaine treatment. Very small amounts of message for all three subunits were evident by day 6 and began to approach normal levels by day 12-15. The mRNA for both the alpha and alpha' subunits of phosphorylase kinase exhibited a similar pattern of recovery, as did also the mRNA for phosphorylase. In contrast to both phosphorylase kinase and phosphorylase, actin mRNA exhibited a quite a different pattern, with a nearly full recovery of message levels by day 6 post-bupivacaine. These data indicate that synthesis of phosphorylase and the alpha, beta, and gamma subunits of phosphorylase kinase appears to be coordinately regulated at the level of message accumulation and that the expression of phosphorylase kinase activity is likely to be also regulated post-transcriptionally.

Amino Acid Sequence↗
PubMed1992

Appearance of alpha 1-adrenergic receptors in soleus muscles from SHR.

The depressed functional capabilities of spontaneously hypertensive rat (SHR) muscles, reported previously (Exp. Neurol. 95: 249-264, 1987), may reflect a decrease in muscle responsiveness to catecholamines occurring as a consequence of exposure to the elevated level of plasma catecholamines in SHR. Responsiveness to applied catecholamines was determined in SHR and Wistar-Kyoto rat (WKY) soleus by measuring muscle resting membrane potentials (RMP) in vitro. Epinephrine (10(-6) M) produced a similar membrane hyperpolarization in SHR and WKY fibers. Pretreatment with the beta-antagonist propranolol completely blocked the epinephrine-induced hyperpolarization in WKY, but not in SHR. SHR soleii from both young and old rats contained a population of alpha 1-adrenergic receptors also associated with membrane hyperpolarization. The alpha-receptors appeared to be associated with a ligand-gated Ca(2+)-influx pathway, since the alpha-agonist-induced membrane hyperpolarization required the presence of Ca2+ in the extracellular medium. The alpha-induced hyperpolarization was also blocked by apamin, a derivative of bee venom which blocks a Ca(2+)-activated K(+)-efflux pathway in a variety of tissues. The possible role of these novel alpha-receptors in skeletal muscle function, and their relationship to the development of hypertension, is uncertain.

Aging↗
PubMed1991

Altered ionic permeability in skeletal muscle from horses with hyperkalemic periodic paralysis.

A recently described disorder in certain registered Quarter horses bears many clinical similarities to the muscle disease identified as hyperkalemic periodic paralysis (HPP) in humans. Pathological changes in membrane permeability or Na(+)-K+ pump activity have been proposed to produce the muscle depolarization and inexcitability that characterize the condition in humans. Biopsies of external intercostal muscle from normal and affected horses were used to determine whether alterations in either permeability and/or pump activity could be linked to the pathology in horses. Affected horse muscle is approximately 16 mV more depolarized than normal muscle at rest, and the muscle membrane potential of HPP horses is less responsive to changes in extracellular K+. Calculation of the relative membrane permeabilities of Na+ and K+ (PNa/PK) indicates that this ratio is significantly increased in HPP muscle. The increase is probably due to an increase in PNa rather than to a decrease in PK, since addition of 10(-6) M tetrodotoxin produces an approximately 14-mV membrane hyperpolarization in HPP fibers but is without effect in normal fibers. The clinical similarities between HPP in horses and humans suggest a common genetic defect in the two species.

Aging↗
PubMed1991

Reduced glycolytic metabolism in regenerated fast-twitch skeletal muscle.

Freely grafted rat extensor digitorum longus (EDL) muscles were subjected to low-frequency stimulation in an anaerobic environment to determine whether regenerating fast-twitch muscles regain normal glycolytic metabolic capacity. Regenerating muscles were tested at 28, 42, and 76 days after the graft procedure. Stabilized grafts (76 days) produced approximately 60% of the lactate generated by intact, control EDL subjected to the same stimulus paradigm and developed half the estimated increase in H+. The grafts exhibited the same relative decline in force after 5 min of anaerobic stimulation as control EDL but maintained relatively constant levels of ATP while consuming phosphocreatine. This study indicates that regenerating fast-twitch skeletal muscle has a reduced ability to initiate glycolytic activity during exercise. The data also indicate that a small population of regenerating fast-twitch fibers express the slow isoform of myosin heavy chain (beta-MHC) with maximum expression occurring at 56 days postsurgery.

Adaptation, Physiological↗
PubMed1991

Apparent upregulation of Na+,K+ pump sites in SHR skeletal muscle with reduced transport capacity.

Slow-twitch, oxidative skeletal muscles in SHR exhibit several physiological defects, including a reduced ability to maintain force during high frequency repetitive stimulation (1). Muscle fatigue may be produced by one of a variety of factors acting at different levels of the neuromuscular system. Several lines of evidence, however, suggest that SHR soleus fatigues more rapidly than WKY soleus because SHR muscles allow more K+ to accumulate in the extracellular space during repetitive muscle activity. An increase in extracellular K+ can lead to a failure in the generation or conduction of muscle action potentials. Comparison of the compound action potentials recorded from SHR and WKY muscles during repetitive stimulation provided evidence for a decrease in excitability of SHR soleus. Since the K+ released from muscle fibers during exercise is returned to the fiber principally via the activity of the Na+, K+ pump, the increase in extracellular K+ in SHR muscle may reflect a decrease in pump capacity. Measurements including intracellular K+ and Na+ content at rest, the level of hyperpolarization produced by the addition of epinephrine and insulin to SHR soleus and the post-exercise recovery of resting membrane potentials all appear to indicate that Na+, K+ pump capacity is reduced in SHR soleus muscles. Nonetheless, ouabain binding studies show a significantly greater number of pump sites in SHR muscles. The data suggest that Na+ pump activity is decreased in SHR soleus muscles without an apparent reduction in either the number of pump sites or in pump binding affinity.

Animals↗
PubMed1989

Beta-receptor properties in soleus muscles from spontaneously hypertensive rats.

We have compared the properties of beta-adrenergic receptors in slow-twitch, oxidative skeletal muscles (soleus) from spontaneously hypertensive rats (SHR) and Wistar-Kyoto (WKY) rats at three different ages. The investigation was based on the hypothesis that the increase in Na+ content and decrease in fatigue resistance observed previously in the soleus of SHR might be the result of a down regulation of muscle beta-receptors. Activation of beta-adrenergic receptors in skeletal muscle stimulates sarcolemmal sodium-potassium adenosine triphosphatase, which produces an efflux of Na+ and an influx of K+. Receptor down-regulation would be expected to reduce hormonal stimulation of Na+ pump activity, particularly during exercise. The results of receptor binding studies, however, and an investigation of cyclic adenosine monophosphate (cAMP) production in response to applied epinephrine indicated that there were no significant differences in receptor properties in the soleus muscles of SHR and WKY rats. Receptor number and affinity were the same in the two strains, and the rate, magnitude, and duration of the increase in cAMP in response to 10(-6) M epinephrine were also similar. beta-Adrenergic receptor down-regulation does not appear to be a generalized phenomenon in tissues of SHR, despite the appearance of other physiological changes in the tissue.

Animals↗
PubMed1988

Cranial components of startle behavior in larval and adult lampreys.

Larval lampreys (Petromyzon marinus) exhibit a combination of cranial reflexes during their vibration-evoked startle response, including strong contractions of the gill chamber, velum and oral hood. These reflexes were confirmed by applying brief vibratory stimuli to an otic capsule and recording movement and electromyograms in moving preparations and efferent cranial nerve activity in curarized preparations. Vibration elicited efferent discharge in cranial nerves V, IX and X on both sides. The responses were lost following labyrinthectomy. The larval startle response results in water from the contracting gill chamber being expelled through the mouth and temporarily reduces head width. Reduced head width may facilitate the rapid withdrawal which is observed during startle behavior in burrowed larvae [S. Currie (1985) Neurosci. Abstr. 11, 268; S. Currie and R. C. Carlsen J. exp. Biol. (in Press)]. Adult lampreys (Entosphenus tridentata) attached to the wall of an aquarium by their suctorial disc, exhibited a brief but intense suction increase following a vibratory stimulus initiated by a tap to the aquarium wall. Oral suction (negative pressure) ranged from -0.6 to -10 cm H2O at rest and increased to values as high as -160 cm H2O during the vibration response. Suction intensity increased in direct proportion to the amplitude of the vibratory stimulus. Most of the suction response was lost following labyrinthectomy. Electromyographic recordings from the pharyngeal dilator m. basilaris and the lingual retractor m. cardioapicalis revealed stimulus-locked activity which preceded increased suction in adults, however, no vibration-evoked electromyogram responses were noted while recording from the gill chamber musculature or funnel. Stimulus-locked efferent activity was observed in the V-basilaris and V-apicalis branches of both trigeminal nerves following vibration of an otic capsule. Efferent vibration-evoked activity was lost in the trigeminal nerve after labyrinthectomy. No vibration-evoked activity was observed in nerves IX or X. Sudden vibration evoked dramatically different responses in larval and adult lampreys. Larvae contracted their gill chambers and expelled water from their mouths while adults exhibited a powerful suction reflex and no gill contraction. The trigeminal components of these behaviors (including velum and oral hood movement in larvae, pharynx and apicalis movement in adults) are difficult to compare. All of the larval trigeminal muscles degenerate during metamorphosis and are replaced by new adult muscles [M. W. Hardisty and C. M. Rovainen (1982) In The Biology of Lampreys, Vol. 4A. Academic Press, London].(ABSTRACT TRUNCATED AT 400 WORDS)

Animals↗
PubMed1988

Pharmacologic enhancement of functional recovery in free muscle transfers.

To date, most free muscle transfers have been marginally successful as functioning units, producing no more than 50 percent of the tension generated by an identical non-transferred muscle. Functional recovery depends both on revascularization and re-innervation, even after careful microvascular anastomosis, remains limited. Forskolin is a robust stimulator of adenylate cyclase and has been used to stimulate peripheral nerve regeneration in vivo; Forskolin may also directly increase capillary growth. Chronic infusion of Forskolin for the first 21 days following orthotopic transplantation of rabbit rectus femoris, with neurovascular anastomosis, stimulated a two-fold increase in the force-generating capacity of the transplant nine to 10 months after surgery. These results, in a model similar to clinical free muscle transfer, offer promise that Forskolin treatment can improve functional recovery by improving muscle re-innervation.

Animals↗
PubMed1988

Calcium-dependent regulation of phosphorylase activation in a fast-twitch oxidative-glycolytic skeletal muscle.

Calcium-mediated phosphorylase kinase activation has been studied in the rat flexor digitorum brevis, a fast-twitch oxidative-glycolytic skeletal muscle that exhibits a robust inward Ca2+ current [Can J. Physiol. Pharmacol. 63:958-965, 1985]. This system provided an opportunity to compare the regulation of contraction and activation of phosphorylase by extracellular and intracellular sources of Ca2+. In muscles repetitively stimulated at 21 degrees, there appeared to be a close correlation between the control of contraction and phosphorylase activation. Blocking extracellular Ca2+ entry promoted an inactivation of phosphorylase and diminished the elevation of resting tension, which in untreated muscles ensues with the onset of fatigue. The response of muscles stimulated at 37 degrees was in distinct contrast. Phosphorylase, following initial rapid activation, was then briskly inactivated despite the continuation of a near-maximal contractile response. An elevation in resting tension during stimulation was observed at 37 degrees but was a transitory response in comparison to what was seen at 21 degrees. Blocking the entry of external Ca2+ inhibited this response. Sarcolemmal Ca2+ channel blockers had no effect on the observed phosphorylase response at 37 degrees, but phosphorylase was already nearly fully inactivated before their effects were manifested on contraction. Thus, at this temperature there is a clear dissociation between Ca2+-mediated regulation of contraction and the production of metabolic energy by enhanced glycogenolysis. This appears to occur because, although Ca2+ induces phosphorylase activation, a subsequent, but rapid non-Ca2+-mediated event promotes inactivation, even while Ca2+-mediated contraction is being sustained.

Animals↗
PubMed1987

Characterization of the isolated rat flexor digitorum brevis for the study of skeletal muscle phosphorylase kinase phosphorylation.

The flexor digitorum brevis skeletal muscle, a nearly homogeneous fast-twitch oxidative glycolytic fiber type, has been examined for its suitability to explore the regulation of phosphorylase kinase by multisite phosphorylation. A characterization of the adrenergic response of glycogenolytic enzymes, together with the previous data on contractile properties (Carlsen, R. C., Larson, D. B., and Walsh, D. A. (1985) Can. J. Physiol. Pharm. 63, 958-965), has demonstrated that this muscle is stably maintained for the several hours necessary for phosphorylation studies. The phosphorylase kinase in this muscle is primarily the alpha' isozyme, suggesting that the alpha versus alpha' isozyme distribution in muscle is related more to oxidative capacity than to fiber contractile characteristics. Using this muscle system, beta-adrenergic activation of phosphorylase kinase was observed to occur with concomitant phosphorylation of both the alpha' and beta subunits, with the total in the alpha' subunit being approximately 3-fold greater. Similarly, deactivation, following initial adrenergic activation, occurred concomitantly with the dephosphorylation of the two subunits. These results are compatible with the conclusions drawn from previous studies of the isolated enzyme and of the enzyme in perfused rat cardiac muscle, that both alpha' (or alpha) and beta subunit phosphorylation regulate phosphorylase kinase activity.

Adenosine Triphosphate↗
PubMed1987

Decrease in force potentiation and appearance of alpha-adrenergic mediated contracture in aging rat skeletal muscle.

The effect of increasing age on contractile performance and catecholamine receptor activity was investigated in a distal, predominantly fast twitch oxidative glycolytic (FOG) muscle from the plantar surface of the rat hindfoot. The ability of the flexor digitorum brevis (FDB), isolated from anesthetized rats and maintained in vitro, to undergo post-tetanic potentiation and a staircase response declined with age. Potentiation following repetitive stimulation was reduced by 50% in 2 year old rats and eliminated in 3 year old animals. The rate of muscle fatigue during intermittent tetanic stimulation also increased in aging muscles. FDB, regardless of age, did not develop a positive inotropic response to 10(-6) M epinephrine applied in vitro, but 3 year old FDB generated a prolonged contracture. Contracture tension was approximately 25% of twitch tension and was maintained for 2-10 min in the continued presence of catecholamine. Contractures were eliminated by pretreatment with alpha-adrenergic antagonists or by removing Ca2+ from the bathing medium. In addition to decreased contractile capacity, aging muscles acquire a population of alpha-adrenergic receptors which may underlie some of the metabolic and structural changes associated with increasing age.

Aging↗
PubMed1987

Decline of isometric force and fatigue resistance in skeletal muscles from spontaneously hypertensive rats.

Skeletal muscles from 6- to 7-month-old male spontaneously hypertensive rats showed a decrease in functional capacity compared with muscles from age-matched normotensive Wistar-Kyoto rats. Predominantly slow-twitch, oxidative soleus muscles developed less force (normalized to muscle wet weight) and were less resistant to fatigue. Heterogeneous, but largely fast-twitch, oxidative-glycolytic medial gastrocnemius muscles generated less force, were smaller in size (normalized to body weight), and did not demonstrate the same degree of stimulation-associated potentiation (staircase effect) as did the medial gastrocnemius of the normotensive rats. The reduced endurance of the soleus of hypertensive rats was not associated with either fiber redifferentiation or capillary "rarification," and the majority of the decline in force with time could not be attributed to impaired neuromuscular transmission. The decrease in muscle capacity in the spontaneously hypertensive rat, thus, appears to be the result of adaptive changes localized in the muscle cells themselves. The adaptive changes, regardless of site, have a pronounced negative effect on muscle function, and could significantly influence motor performance and antihypertensive therapy.

Action Potentials↗
PubMed1987

Chronic infusion of agents that increase cyclic AMP concentration enhances the regeneration of mammalian peripheral nerves in vivo.

Our previous investigation indicates that forskolin, a robust activator of adenylate cyclase, promotes sensory nerve regeneration in amphibians. The present study was designed to determine if forskolin had a similar effect in mammals. We also wished to test the hypothesis that cyclic AMP modulates nerve regeneration by comparing the effects of chronically infused forskolin with the effects of infused dibutyryl cyclic AMP, 8-bromo cyclic AMP, and the phosphodiesterase inhibitor, theophylline. Our results indicated that all agents promoted some aspect of regeneration. The two which presumably generated the largest increase in cyclic AMP concentration, forskolin and 8-bromo cyclic AMP, had the most profound effect on axonal elongation. All agents decreased the time to sprout initiation, but theophylline produced the largest decrease and its effect was mimicked by caffeine, a methylxanthine with limited ability to inhibit phosphodiesterase. This suggests that sprout formation may be triggered by an increase in intraaxonal free Ca2+, possibly modulated by cyclic AMP. The role of cyclic AMP in axonal elongation remains to be determined, but may be associated with stimulation of protein synthesis in the nerve cell body.

8-Bromo Cyclic Adenosine Monophosphate↗
PubMed1987

Recovery of free muscle grafts in rat: improvement is associated with an increase in cyclic adenosine monophosphate concentration or use of the condition/test paradigm.

The muscle fibers in freely grafted skeletal muscles degenerate and are replaced by new fibers which develop within the graft. Myogenesis in regenerating muscle recapitulates, to a large extent, developmental myogenesis and may depend on similar modulating influences. In addition to the generation of new fibers, functional recovery of free muscle grafts also requires reinnervation and revascularization of the new fibers. Recovery of function should be improved by enhancing either myogenesis or reinnervation and revascularization. We have used two procedures, shown previously to stimulate peripheral nerve regeneration, to improve the morphologic and functional recovery of free, orthotopic grafts of rat extensor digitorum longus muscle. Each of the procedures was effective, but had potentially different sites of action. The first procedure, the condition/test paradigm, presumably increases the rate and extent of graft reinnervation. The second procedure, continuous infusion of the adenylate cyclase activator forskolin during the first 21 days after grafting, may influence both myogenesis and nerve regeneration. Each procedure increased regenerating muscle fiber size and functional capacity, and forskolin also significantly increased capillary density and fatigue resistance.

Animals↗
PubMed1987

Modulated vibration-sensitivity of lamprey Mauthner neurones.

The vibration-sensitivity of larval lamprey Mauthner (Mth) neurones is dependent on behavioural state. Animals are maximally vibration-sensitive when at rest and less so when active or aroused. To demonstrate this effect in freely behaving larvae, we provided repeated vibratory or electrical stimuli to the vestibular labyrinths while animals made transitions between rest and activity. Stimuli which were adequate to elicit Mth spikes 100% of the time in a resting animal (recorded extracellularly from the spinal cord) were consistently subthreshold while the animal was swimming. The same effect was seen in semi-intact preparations, both moving and curarized, while recording intracellularly from Mth cell bodies. Mth vibration-sensitivity decreased abruptly with the onset of 'arousal', defined here by the presence of tonic, descending spinal cord discharge. During arousal, the Mth soma exhibited a slight depolarization (2-8 mV), an increased membrane conductance, and a strong depression of vibration-evoked excitatory postsynaptic potential (EPSP) amplitude. This Mth PSP depression (MPD) appears to underlie altered vibration-sensitivity.

Animals↗
PubMed1987

Functional significance and neural basis of larval lamprey startle behaviour.

1. The vibration-evoked startle response mediates rapid withdrawal in burrowed larval lampreys (ammocoetes). Ammocoetes withdraw in response to vibration by contracting pre-existing lateral bends in the trunk and tail, thus pulling their heads deeper into the burrow. 2. The motor effects of an ammocoete startle response are dependent on pre-existing posture. Areas of lateral body curvature contract more and exhibit larger electromyogram (EMG) amplitudes on their inner sides than on their outer sides. 3. Both of the anterior Mth and posterior Mth' (Mauthner) cells and both of the B1 and B2 (bulbar) Müller cells fired action potentials in response to vibration of the otic capsules. Both B3 and B4 Müller cells were inhibited by vibration, while M (mesencephalic) and I1 (isthmic) Müller cells were inhibited by ipsilateral vibration and excited by contralateral vibration. 4. Simultaneous action potentials in both of the anterior Mth cells were appropriate and sufficient for initiating the startle response EMG in a semi-intact preparation. 5. This study demonstrates a Mauthner-initiated startle response which activates musculature on both sides of the body to produce a rapid withdrawal movement and is thus adapted to the eel-like form and burrowed lifestyle of larval lampreys.

Action Potentials↗
PubMed1985

A rapid startle response in larval lampreys.

Electromyography (EMG) and cinematography revealed a rapid, vibration-evoked startle response in intact larval lampreys. Vibratory stimuli produce simultaneous contraction of both sides of the body, and the response is lost after labyrinthectomy. Midbody EMGs exhibit a stimulus-response latency of 26.5 +/- 4.2 ms. Direct stimulation of the otic capsules, using an electrically driven probe applied to a semi-intact preparation, first evokes a volley of giant axon spikes in the spinal cord followed by the bilateral trunk response.

Animals↗