tetrodotoxin and Myotonia

The myotonic activity of mouse soleus and extensor digitorum longus muscles induced by either a combination of K+ channel blockers (4-aminopyridine) and a Cl- channel blocker (9-anthracene carboxylic acid) or a Cl- channel blocker in low Ca2+ (0.25 mM) Krebs or a Na+ channel activator (veratridine) was characterized in this paper. Myotonic activity was characterized by an increase in both the contraction amplitude and contraction duration accompanied by stimulus-related repeated action potentials. The slow soleus and fast extensor digitorum longus muscles appeared to differ in their responses to these ion channel modifiers. Nevertheless, chlorpromazine at a low concentration of 1 microM significantly inhibited all kinds of myotonic activity; it reduced the prolonged contraction duration and attenuated the stimulus-related repeated action potential firing. This depressant action of chlorpromazine was apparently not correlated with inhibition of either calmodulin or phospholipase A2 activity, since the myotonic depressant action of calmodulin inhibitors, such as dibucaine, flunarizine, chlorpromazine, trifluoperazine and diltiazem, was unrelated to their potency in inhibiting the activity of calmodulin or phospholipase A2. However, phosphatidylcholine was found to inhibit the myotonic depressant action of chlorpromazine. It is therefore, tentatively concluded that chlorpromazine interacted with membrane phospholipids, thereby changing membrane ion channel activity and depressing myotonic activity. These findings indicate that chlorpromazine might be useful in the management of clinical myotonia.

Topics: 4-Aminopyridine; Action Potentials; Animals; Chlorpromazine; Elapid Venoms; Ion Channels; Isotonic Solutions; Membrane Potentials; Mice; Mice, Inbred ICR; Microelectrodes; Muscles; Myotonia; Phospholipases A; Phospholipases A2; Tetrodotoxin; Veratridine

Topics: Action Potentials; Animals; Azacosterol; Cholesterol; Male; Membrane Potentials; Muscle Contraction; Muscles; Myotonia; Ouabain; Potassium; Rats; Rats, Inbred Strains; Sodium; Tetrodotoxin

Topics: Action Potentials; Aging; Animals; Disease Models, Animal; Electric Conductivity; Goats; Muscle Development; Muscles; Myotonia; Tetrodotoxin

Myotonic discharges in rats given 20, 25-diazacholesterol hydrochloride and fibrillation discharges in denervated rat muscle both were silenced by procaine hydrochloride, tetrodotoxin or ischemia, or potassium chloride (after initial activation). They both were activated by succinylcholine, but only the fibrillations were silenced by alpha-bungarotoxin or atropine sulfate. It is hypothesized that fibrillations and diazacholesterol-induced myotonia are mediated through mechanisms involving ionic channels, that both can be produced by activation of the junctional/nonjunctional acetylcholine receptors (or some mechanism coupled to the receptors), but that an unfettered alpha-bungarotoxin-binding portion of the acetylcholine-receptor molecule and an unblocked atropine-binding site are obligatory only for production of fibrillations.

Topics: Acetylcholine; Animals; Atropine; Azacosterol; Bungarotoxins; Evoked Potentials; Ischemia; Male; Muscle Denervation; Muscle Spasticity; Muscles; Myotonia; Potassium Chloride; Procaine; Pyridostigmine Bromide; Rats; Receptors, Cholinergic; Succinylcholine; Tetrodotoxin; Tubocurarine