NEURAL CONTROL OF THE EXPRESSION OF A CA2-ACTIVATED K+ CHANNEL INVOLVED IN THE INDUCTION OF MYOTONIC-LIKE CHARACTERISTICS()

1. Expression of the apamin-sensitive K+ channel (SK+) in rat skeletal muscle is neurally regulated. The regulatory effect of the nerve over the expression of some muscle ion channels has been attributed to the electrical activity triggered by the nerve and/or to a trophic effect of some molecules transported from the soma to the axonal endings. 2. SK+ channels apparently are involved in myotonic dystrophy (MD), ther efore understanding the factors that regulate their expression may ult imately have important clinical relevance. 3. To establish if axoplasm ic transport is involved in this process, we used two experimental app roaches in adult rats: (a) Both sciatic nerves were severed, leaving a short or a long nerve stump attached to the anterior tibialis (AT). ( b) Colchicine or vinblastine (VBL), two axonal transport blockers of d ifferent potencies, was applied on one leg to the sciatic nerve. To de termine whether electrical activity affects the expression of SK+ chan nels, denervated AT were directly stimulated. The corresponding contra lateral muscles were used as controls. 4. With these experimental cond itions we measured (a) apamin binding to muscle membranes, (b) muscle contractile characteristics, and (c) electromyographic activity. 5. In the short- and long-nerve stump experiments, 5 days after denervation I-125-apamin binding to AT membranes was 2.0 times higher in the shor t-stump side. This difference disappeared at longer times. The delayed expression of SK+ channels in the muscle left with a longer nerve stu mp can be attributed to the extra axoplasm contained in the longer stu mp, which maintains a normally repressive signal for a longer period o f time. Ten to 15 days after application of axonal transport blockers we found that the muscle half-relaxation time increased in the drug-tr eated side and apamin partially reverted the prolonged relaxation. Myo tonic-like discharges specifically blockable by apamin were always pre sent in the drug-treated leg. I-125-Apamin binding, which is undetecta ble in a microsomal preparation from hind leg control muscles, was inc reased in the drug-treated preparations. Apamin binding to denervated and stimulated AT muscles was lower than in the contralateral unstimul ated muscles [3.3 +/- 1.0 vs 6.8 +/- 0.8 (n = 4) fmol/mg protein]. 6. Our results demonstrate that electrical activity and axoplasmic transp ort are involved in the control of expression of SK+ in rat skeletal m uscle. However, the increased expression of this channel induces myoto nic-like characteristics that are reversed by apamin. This myotonic ac tivity could be a model for MD.