Changes in Na channel properties of frog and rat skeletal muscles induced by the AaH II toxin from the scorpion Androctonus australis.
The effects of the mammal toxin II isolated from the venom of the scorpion Androctonus australis Hector (AaH II) were studied under current and voltage clamp conditions in frog (semitendinosus) and rat (fast e.d.l. and slow soleus) skeletal twitch muscle fibres. In both species, AaH II induced a dose-dependent prolongation of the action potential (AP) leading at saturating concentration to APs with long plateaus of about 1.5 s in frog and 5 s in rat e.d.l. and soleus fibres. The concentrations to induce 50% of the maximal effect (K0.5) were 9.1 x 10(-9) M in the frog and 1.4 x 10(-9) M in the rat. AaH II increased the time constants of inactivation of the peak Na current and induced a maintained Na current that was greater in rat e.d.l. and soleus (31.6% of peak current amplitude at -30 mV; K0.5 = 0.8 x 10(-9) M) than in frog (16.5%; K0.5 = 15.5 x 10(-9) M) muscles. Peak and maintained Na currents were TTX-sensitive and had identical threshold and reversal potentials. The half-maximum maintained permeability occurred at a potential 20 mV more positive than the peak permeability. Recovery from inactivation and steady-state inactivation of the inactivating Na current remained unchanged. The maintained current deactivated with normal fast kinetics. The action of the toxin reversed poorly on washout but could be largely removed by conditioning depolarizations more positive than the reversal potential of the Na current. Our results suggest that, in vertebrate skeletal muscle fibres, AaH II affects all the Na channels and are consistent with the hypothesis that the maintained current originates from a reopening of previously inactivated Na channels.
Duval
A
A
CNRS URA 611, Université d'Angers, France.
Malécot
C O
CO
Pelhate
M
M
Rochat
H
H
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002463:Cell Membrane Permeability / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D008564:Membrane Potentials / Q000187:drug effects; D009132:Muscles / Q000187:drug effects / Q000378:metabolism*; D009498:Neurotoxins / Q000494:pharmacology*; D011893:Rana esculenta; D051381:Rats; D030162:Reptilian Proteins; D012604:Scorpion Venoms / Q000494:pharmacology*; D012964:Sodium / Q000378:metabolism; D015222:Sodium Channels / Q000187:drug effects / Q000378:metabolism*
D009498:Neurotoxins; D030162:Reptilian Proteins; D012604:Scorpion Venoms; D015222:Sodium Channels; C053969:scorpion toxin II, Androctonus; D012964:Sodium