Library

feed icon rss

Your email was sent successfully. Check your inbox.

An error occurred while sending the email. Please try again.

Proceed reservation?

Export
  • 1
    ISSN: 1474-8673
    Source: Blackwell Publishing Journal Backfiles 1879-2005
    Topics: Chemistry and Pharmacology , Medicine
    Notes: 1 Prolonged bed rest or exposure to microgravity may cause several alterations in autonomic nervous system response (ANSR). 2 Hindlimb unloading (HU) rats were used as an animal model of simulated microgravity to investigate ANSR changes. The experiments were carried out to investigate the effects of simulated microgravity on the autonomic nervous response of the perfused mesenteric vascular bed (MVB), vas deferens and the colon and duodenum from 2-week HU rats. 3 In MVB preparations of HU rats, the frequency-dependent increases in perfusion pressure with perivascular nerve stimulation (PNS; 8–40 Hz) were inhibited, whereas the noradrenaline (NA) concentration-dependent (1–100 μm) perfusion pressure increases were potentiated. The latter most probably reflected up-regulation of α-adrenergic receptor function. Relaxant responses of NA-precontracted MVB to PNS (4–30 Hz) or isoprenaline were not different between control and HU preparations, while vasodilation induced by the endothelial agonist ACh was reduced. 4 Transmural stimulation (2–40 Hz) induced frequency-dependent twitches of the vas deferens which were reduced in vas deferens of HU rats, while the sensitivity to NA-induced contraction was significantly increased. 5 In the gastroenteric system of HU rat, direct contractile responses to carbachol or tachykinin as well as relaxant or contractile responses to nervous stimulation appeared unchanged both in the proximal colon rings and in duodenal longitudinal strips. 6 In conclusion, HU treatment affects peripheral tissues in which the main contractile mediators are the adrenergic ones such as resistance vessels and vas deferens, probably by reducing the release of neuromediator. This study validates NA signalling impairment as a widespread process in microgravity, which may most dramatically result in the clinical phenotype of orthostatic intolerance.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 2
    Electronic Resource
    Electronic Resource
    Amsterdam : Elsevier
    Regulatory Peptides 10 (1985), S. 226 
    ISSN: 0167-0115
    Source: Elsevier Journal Backfiles on ScienceDirect 1907 - 2002
    Topics: Medicine
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 3
    ISSN: 1432-2013
    Keywords: Rat skeletal muscle ; Development ; Chloride channels ; Anthracene 9-carboxylic acid ; Contractile properties
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract A specific chloride channel blocker, anthracene 9-carboxylic acid was locally applied for 8–9 days on the extensor digitorum longus muscle of 7–8-day-old rats. The effects of chronic anthracene 9-carboxylic acid treatment on muscle development, were evaluated in vitro on the electrical properties with intracelluar microelectrodes and in vivo on the contractile parameters by recording isometric concentractions. Our data show that the treatment prevented the normal development of chloride conductance so that by 15 days of age it was 45% lower in fibers of the treated muscles when compared to age-related control fibers. Potassium conductance was not significantly changed by the treatment. In vivo the anthracene-9-carboxylic acid-treated muscles were slower to contract and relax; having a 20% slower time to peak twitch force and time of half relaxation. These muscles were also 32% less fatiguable with respect to the controls. Moreover, in most of the treated muscles tetanic contractions during high-frequency stimulation were not maintained. The block of chloride channels in developing striated fibers appears to affect the differentiation of specific properties of fast skeletal muscle such as the speed of contraction.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 4
    ISSN: 1432-2013
    Keywords: Antiarrhythmic drugs ; Sodium channels ; Molecular modelling ; Human muscle ; Whole-cell recording
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of both enantiomers of tocainide and of some of its chiral analogs on the inactivation of the sodium current in human myoballs were investigated with the whole-cell recording technique. Structure and electron densities of the applied compounds were calculated and compared to the results. Both the R(−) and the S(+) enantiomers had little effect on fast inactivation determined with short prepulses according to Hodgkin and Huxley (1952; h ∞ curve). When the inactivating prepulses used in this pulse protocol were prolonged to 1024 ms, both tocainide enantiomers increased inactivation severely, suggesting that the drug binds to the channel when it is in the state of intermediate inactivation (Fakler et al. 1990). Tetrodotoxin-resistant “juvenile” sodium channels were more affected than tetrodotoxin-sensitive “adult” channels. The R form was four times as effective as the S form. The compound obtained by substitution of the methyl group on the chiral centre of tocainide with a benzyl group, although in the less potent S form, affected inactivation of the juvenile sodium channels much more than the potent (R)-tocainide. Two additional substitutions, performed on the aromatic ring of tocainide, gave a compound that was most potent in shifting the inactivation curves, but without any selectivity for juvenile or adult channels.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 5
    ISSN: 1432-2013
    Keywords: Rat skeletal muscle ; Phorbol esters ; Staurosporine ; Protein kinase C ; Chloride channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The membrane electrical parameters and component conductances of rat extensor digitorum longus muscle fibres were studied in vitro at 30 °C with standard two microelectrode square pulse cable analysis in the presence of protein kinase C (PKC) activators and inhibitors. The PKC activator, 4-β-phorbol-12,13 dibutyrate (4-β-PDB), (2–90nM) blocked up to 67% chloride conductance (G Cl) in rat skeletal muscle fibres and induced myotonic hyperexcitability. The concentration necessary to produce a 50% block of the membrane G Cl was 23 nM. The “inactive” 4-α-phorbol-12,13 dibutyrate had no effect at 2 μM. The blocking effect of 4-β-PDB on G Cl was prevented by preincubation of the preparations with the PKC inhibitors, staurosporine (1–5 μM) and tetrahydropapaverolone (50–100 μM). The blocking effects on membrane G Cl of 4-β-PDB and its antagonism by the inhibitors used support the concept of the involvement of PKC in regulating Cl channels of mammalian skeletal muscle fibres.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 6
    ISSN: 1432-2013
    Keywords: Chloride channel ; Rat ; Skeletal muscle ; Stereoisomers ; 2-(p-chloro-phenoxy) isobutyric acid ; Clofibric acid ; Myotonia
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The S-(−) isomers of a series of clofibric acid analogs produced only a block of chloride conductance of rat skeletal muscle fibers with increasing concentrations until block was nearly complete. The R-(+) isomers, on the other hand, at low concentrations increased chloride conductance by as much as 9% to 39% and at higher concentrations decreased chloride conductance, but never by more than 27% of the control value. The actions of the enantiomeric pairs to either produce or inhibit myotonic excitability paralleled their ability to block or increase chloride conductance, respectively.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 7
    ISSN: 1432-1912
    Keywords: Sodium channel ; Excitability ; Skeletal muscle ; Enantiomers ; Mexiletine ; Tocainide ; Use-dependent block ; Myotoma
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract The effects of the enantiomers of mexiletine were tested on sodium currents of frog skeletal muscle fibers recorded by means of the three vaseline gap voltage clamp method and compared with the effects produced by tocainide enantiomers. The R-( − ) mexiletine produced a tonic block of the sodium current, elicited by single depolarizing test pulses from the holding potential of − 100 mV to − 20 mV, with an IC50 of 43.9 ± 1 μM, whereas the corresponding S-( + ) enantiomer produced the same effects at about twofold higher concentrations. A similar stereoselectivity was observed with tocainide enantiomers, but at about 5 fold higher concentrations. Both the R-( − ) and S-( + ) enantiomers of mexiletine and tocainide produced a further use-dependent block of sodium currents when the test pulse was applied repetitively at a frequency of 2 Hz. The use dependent behaviour led to a significant lowering of the IC50 values with respect to the tonic block but the eudismic ratios ([IC50S-( + )]/[IC50R( − )]) and the relative potency between mexiletine and tocainide were maintained. All the tested compounds produced a left shift of the steady state inactivation curves (h∞) , suggesting a high-affinity interaction with the inactivated sodium channels. Again a stronger potency of R-( − ) vs. S-( + ) enantiomers and of mexiletine vs. tocainide was observed. The excitability characteristics recorded from the semitendinosus muscle by the two microelectrode technique were modified by the tested drugs in agreement with their ability to block sodium current. Thus a concentration-related increase in the threshold current required to elicit an action potential was observed along with a decrease in the amplitude and a shortening of the latency of action potential and a decrease in the firing capability of the membrane. Again the R-( − ) isomers were more potent than the S-( + ) ones and mexiletine was more effective than tocainide. These data corroborate the presence of a stereospecific site for these drugs on adult skeletal muscle sodium channels. The constant eudismic ratios between the enantiomers during both tonic and use-dependent block suggest that the increase in the apparent affinity of the receptor during statedependent conformational changes of the channel does not enhance its stereospecificity. The decrease in effective concentration upon high frequency stimulation supports the potential usefulness of low doses of R-( − ) mexiletine in the treatment of the abnormal hyperexcitability of the myotonic muscles, with a likely reduction of unwanted side effects.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 8
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 417 (1991), S. 605-610 
    ISSN: 1432-2013
    Keywords: Myotonic goat ; Phorbol esters ; Protein kinase C ; Chloride channels
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract External intercostal muscle biopsies from normal and congenitally myotonic goats were studied in vitro at 30° C using a two-microelectrode square-pulse cable analysis assisted by computer. The resting chloride conductance (G cl) was estimated from the difference between the mean membrane conductance in chloride-containing and chloride-free bathing media. The protein kinase C (PKC) activator, 4-β-phorbol-12,13-dibutyrate, (0.1–2.0 μM) blocks a maximum of 76% of G cl in normal goat fibers and induces myotonic hyperexcitability similar to that of congenitally myotonic goat fibers. The G cl block was partially antagonized by pretreatment with the PKC inhibitor, staurosporine (10 μM). The “inactive” 4-αphorbol-12, 13,didecanoate had no effect at 50 μM, whereas the “active” 4-β isomer blocked 41% G cl at 1 μM. The nearly absent G cl of congenitally myotonic goat fibers was not restored by treatment with high concentrations of the PKC inhibitors staurosporine, 1-(5-isoquinolinesulfonyl)-2-methylpiperazine (H7), or tetrahydropapaveralone (THP). Also, forskolin and cholera toxin, which may increase cyclic adenosine monophosphate (cAMP) levels, or the R(+) clofibric acid enantiomers and taurine, which increase G cl in normal fibers, were also unable to restore G cl in myotonic goat fibers. The data suggest that PKC may be a chloride channel regulator in normal goat skeletal muscle fibers, however the molecular defect of congenitally myotonic fibers does not appear to be due to excessive activity of PKC.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 9
    ISSN: 1432-2013
    Keywords: Key words Hypokalaemic periodic paralysis ; ATP-sensitive K+ channels ; Insulin ; Skeletal muscle ; Patch clamp
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract  In the present work, we examined the effects of in vivo administration of insulin to rats made hypokalaemic by feeding a K+-free diet. The i.p. injection of insulin in the hypokalaemic rats provoked muscle paralysis within 3–5 h. Consistent with this observation, the skeletal muscle fibres of the paralysed rats were depolarized. In contrast, in the normokalaemic animals, insulin neither provoked paralysis nor produced significant fibre hyperpolarization. In the hypokalaemic rats, insulin almost completely abolished the sarcolemma adenosine triphosphate (ATP)-sensitive K+ currents without altering the sensitivity of the channels to ATP or glibenclamide. In contrast, in the normokalaemic rats, insulin enhanced ATP-sensitive K+ currents that became also resistant to ATP and glibenclamide. Our experiments indicate that the modulation of the sarcolemma ATP-sensitive K+ channels by insulin is impaired in the hypokalaemic state. This phenomenon appears to be related to the fibre depolarization and paralysis observed in the same animals.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
  • 10
    Electronic Resource
    Electronic Resource
    Springer
    Pflügers Archiv 427 (1994), S. 80-85 
    ISSN: 1432-2013
    Keywords: Rat skeletal muscle ; Aging ; Chloride channels ; Phorbol esters ; Protein kinases ; Cholera toxin ; G protein pathways ; Calcium ionophore A23187
    Source: Springer Online Journal Archives 1860-2000
    Topics: Medicine
    Notes: Abstract By the use of pharmacological tools, we tested the hypothesis that age-related alterations in the regulatory pathways of chloride channels might contribute to the lowered chloride conductance (G Cl) found in skeletal muscle of aged rats. The restingG Cl of extensor digitorum longus (EDL) muscles from adult rats either young (3–4 months old) or aged (29 months old) was measured by means of computerized intracellular microelectrode recordings. In EDL muscle from 3 to 4-month-old rats, 4-β-phorbol 12,13-dibutyrate (4-β-PDB), a direct activator of protein kinase C (PKC), decreasedG Cl in a concentration-dependent manner. The same effect was exerted by cholera toxin. The effects of both the phorbol ester and cholera toxin were inhibited by staurosporine, thus indicating that either direct or indirect (via G protein) activation of PKC accounts for the decrease ofG Cl. An increase of cytosolic Ca2+ by the ionophore A23187 also significantly decreasedG Cl by 25%. In EDL muscles from aged rats, 4-β-PDB was 20-fold more potent in blockingG Cl than in muscles from younger controls, and the ionophore blockedG Cl by 40%. On the other hand, cholera toxin was ineffective. Our findings support the hypothesis that in fast-twitch muscle the regulation of chloride channels by PKC and Ca2+ is a target of the aging process.
    Type of Medium: Electronic Resource
    Library Location Call Number Volume/Issue/Year Availability
    BibTip Others were also interested in ...
Close ⊗
This website uses cookies and the analysis tool Matomo. More information can be found here...