ISSN:
1432-2013
Schlagwort(e):
Myotonic goat
;
Phorbol esters
;
Protein kinase C
;
Chloride channels
Quelle:
Springer Online Journal Archives 1860-2000
Thema:
Medizin
Notizen:
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.
Materialart:
Digitale Medien
URL:
http://dx.doi.org/10.1007/BF00372958
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