Supersensitivity of skeletal muscle produced by botulinum toxin

Thesleff, S.

doi:10.1113/jphysiol.1960.sp006463

Cited by 319 publications

(127 citation statements)

References 15 publications

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“…Consistent with previous reports (13,43), there were no obvious structural abnormalities in botulinum-intoxicated nerves. Like normal unstimulated nerves, toxin-treated ones contained small mitochondria with dense internal matrices which lacked electron-dense granules (Fig.…”

Section: Botulinum-intoxicated Neuromuscular Junctionssupporting

confidence: 81%

“…One candidate for such a probe of the calcium channel is the neurotoxin produced by Clostridium botulinum. This is a 150,000 mol wt protein which blocks acetylcholine release at the neuromuscular junction without altering impulse conduction in the motor axon (3,13) and without altering the acetylcholine sensitivity of the muscle membrane (4,40,41,43) . Previous physiological work has raised the possibility that this toxin does indeed block depolarization-induced calcium influx into the terminal (3,13) .…”

mentioning

confidence: 99%

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Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

Hirokawa¹,

Heuser²

1981

The Journal of Cell Biology

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Taking advantage of the fact that nerve terminal mitochondria swell and sequester calcium during repetitive nerve stimulation, we here confirm that this change is caused by calcium influx into the nerve and use this fact to show that botulinum toxin abolishes such calcium influx. The optimal paradigm for producing the mitochondrial changes in normal nerves worked out to be 5 min of stimulation at 25 Hz in frog Ringer's solution containing five times more calcium than normal. Applying this same stimulation paradigm to botulinumintoxicated nerves produced no mitochondrial changes at all . Only when intoxicated nerves were stimulated in 4-aminopyridine (which grossly exaggerates calcium currents in normal nerves) or when they were soaked in black widow spider venom (which is a nerve-specific calcium ionophore) could nerve mitochondria be induced to swell and accumulate calcium . These results indicate that nerve mitochondria are not damaged directly by the toxin and point instead to a primary inhibition of the normal depolarization-evoked calcium currents that accompany nerve activity . Because these currents normally provide the calcium that triggers transmitter secretion from the nerve, this demonstration of their inhibition helps to explain how botulinum toxin paralyzes .

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Section: Botulinum-intoxicated Neuromuscular Junctionssupporting

confidence: 81%

mentioning

confidence: 99%

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

Hirokawa¹,

Heuser²

1981

The Journal of Cell Biology

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“…This may be important, since preliminary observations suggest that the prolonged local application of the toxin in vivo has a direct myotoxic action. This action, which distinguished the Tiger snake toxin from /3-bungarotoxin and botulinum toxin (Thesleff, 1960) is currently being examined. 145 Our results suggest that the acute effect of the purified toxin isolated from the venom of Australian Tiger snake is a reduction in both spontaneous and nerve impulse mediated transmitter release from motor nerve terminals.…”

Section: Discussionmentioning

confidence: 99%

Effects of an isolated toxin from Australian Tiger snake (Notechis scutatus scutatus) venom at the mammalian neuromuscular junction

Harris

Karlsson

Thesleff

1973

British J Pharmacology

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Summary The acute effects of a purified toxin from Australian Tiger snake (Notechis scutatus scutatus) venom have been investigated at the mammalian neuromuscular junction. The toxin was injected into the tail vein of mice. Death was due to respiratory paralysis. The resting membrane potential, and action potential of muscle fibres in muscles from in vivo intoxicated animals were normal. The frequency of miniature end plate potentials (m.e.p.p.s) from intoxicated nerve‐muscle preparations was reduced, although m.e.p.p. amplitude was unaltered. Nerve stimulation resulted in end plate potentials (e.p.p.s) of quantal amplitude; only rarely was the e.p.p. large enough to give rise to an action potential. High (20 mm) K+ did not increase m.e.p.p. frequency in intoxicated preparations. The toxin was largely ineffective in vitro. The similarities and differences between this toxin, β‐bungarotoxin and botulinum toxin are discussed.

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“…Firstly, long-lasting bursts of m.e.p.p.s have been observed following the mechanical injury of motor nerve terminals by a recording micro-electrode. Such volleys occur not only in normal preparations in which a focal depolarization of the terminal will cause the m.e.p.p.s to be released, but also in preparations treated with botulinum toxin (Thesleff, 1960;Boroff, del Castillo, Evoy & Steinhardt, 1974), in which strong depolarization of the nerve endings fails to release any m.e.p.p.s. Secondly, bursts of m.e.p.p.s, often followed by long afterdischarges, have been observed during hyperpolarization of the nerve terminals by applied anodic currents (del Castillo & Katz, 1956).…”

Section: Characteristics Of the Volleysmentioning

confidence: 99%

Discrete and discontinuous action of brown widow spider venom on the presynaptic nerve terminals of frog muscle.

Castillo¹,

Pumplin²

1975

The Journal of Physiology

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Supersensitivity of skeletal muscle produced by botulinum toxin

Cited by 319 publications

References 15 publications

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

Structural evidence that botulinum toxin blocks neuromuscular transmission by impairing the calcium influx that normally accompanies nerve depolarization.

Effects of an isolated toxin from Australian Tiger snake (Notechis scutatus scutatus) venom at the mammalian neuromuscular junction

Discrete and discontinuous action of brown widow spider venom on the presynaptic nerve terminals of frog muscle.

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