Chemically induced myotonia in amphibia

Abstract

Frogs and toads treated with high doses of anthracene-9-carboxylic acid (A-9-C) develop prolonged muscular contractions and 'divebomber' electromyograms characteristic of myotonia. Hitherto, myotonia has been considered peculiar to homeotherms where it is associated with several hereditable diseases and can be induced by specific treatments, most of which seem to act by decreasing membrane chloride conductance. Our work indicates that myotonia can be induced in amphibia by similar means. We offer possible reasons why others have missed seeing myotonia in amphibia.

Extracellular ATP inhibits chloride channels in mature mammalian skeletal muscle by activating P2Y1 receptors

“…Mammalian, but not amphibian, skeletal muscle fibres possess a large t-tubular G Cl (Dulhunty, 1979). Moreover, considerably higher doses and longer exposures to 9AC are required to induce myotonic behaviour in frogs compared to mammals (Bretag et al 1980), suggesting that frogs have a reduced sensitivity to 9AC. These data raise the possibility that the effects of extracellular ATP on mammalian skeletal muscle might be less pronounced or even absent at the frog NMJ.…”

Origin of delayed outward ionic current in charge movement traces from frog skeletal muscle.

“…5B, the residual outward current still rose at the end of the ON segment even though the duration of the TEST pulse was doubled. The retardation caused by 9-ACA made it difficult to quantify the fraction of the Cl-current that disappeared, especially since Bretag, Dawe & Moskwa (1980) reported that 9-ACA is much less potent in blocking Cl-current in amphibian muscle than in mammalian muscle. Prolonging the TEST pulses further generated movement artifacts, even in fibres stretched to a 4 4um sarcomere length.…”

Nav1.4 slow‐inactivation: Is it a player in the warm‐up phenomenon of myotonic disorders?

“…The obvious approach is a mathematical in silico approach, modeling muscular excitation that takes into account both the reduction in chloride conductance (or, conversely, Na v channel gain‐of‐function) and the reduction in available Na v channels during slow‐inactivation . These analyses could be backed up by myotonia animal models, chemical (e.g., the 9‐anthracene carboxylic acid) or genetic (e.g., the ADR mouse), in which slow‐inactivation is pharmacologically enhanced, such as through administration of lacosamide or rufinamide. The slow‐inactivation/warm‐up hypothesis would also be supported if sodium channel myotonia mutations were identified that carry with them severely compromised slow‐inactivation.…”