Increase of apamin receptors in skeletal muscle induced by colchicine: possible role in myotonia.
We have shown an increase of apamin receptors in rat skeletal muscle membranes following the application of colchicine to the sciatic nerve. 125I-apamin binding to partially purified membrane fractions was observed since day 4, reached a maximum around days 6-15, and was negligible at day 35 after the application of colchicine. Control muscles (nerves treated with buffer solution) showed low binding values (11 fmol/mg protein). Maximal 125I-apamin binding values to partially purified muscle membranes of colchicine-treated rats (42 fmol/mg protein) were lower than those obtained in denervated muscle (95 fmol/mg protein). The affinity binding constant values were 37 (colchicine) and 95 pM (denervation). No signs of muscle denervation were observed on histological examination of the nerve submitted to colchicine treatment nor in the muscles innervated by it. Muscle tension developed by indirect stimulation was the same as in controls. We here show also that partially purified membranes of normal untreated muscles have measurable amounts of 125I-apamin binding (13 fmol/mg protein), similar to those obtained in control muscles. Electromyographic recordings of the muscles after colchicine treatment of the nerve showed abnormal repetitive electrical discharges, similar to myotonic discharges, that were present with a similar temporal course as the increase in apamin receptors. The myotonic-like discharges were suppressed by the topical application of apamin to the muscle, whereas the toxin had no effect on anthracene-9-carbolytic acid-induced myotonia. Our results suggest that a neurotrophic factor that travels by axonal flow is involved in the regulation of the expression of apamin receptors in skeletal muscle membranes.(ABSTRACT TRUNCATED AT 250 WORDS)
Behrens
M I
MI
Centro de Estudios Cientificos de Santiago; Hospital Dr. Sótero del Rio, Chile.
Vergara
C
C
D000818:Animals; D001030:Apamin / Q000378:metabolism; D003078:Colchicine / Q000494:pharmacology*; D004576:Electromyography; D008566:Membranes / Q000378:metabolism; D009119:Muscle Contraction; D009121:Muscle Denervation; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009222:Myotonia / Q000503:physiopathology*; D010543:Peroneal Nerve / Q000187:drug effects; D015221:Potassium Channels; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D017981:Receptors, Neurotransmitter / Q000378:metabolism* / Q000502:physiology; D012584:Sciatic Nerve / Q000187:drug effects
D015221:Potassium Channels; D017981:Receptors, Neurotransmitter; C033799:apamin receptor; D001030:Apamin; D003078:Colchicine