Differential effects of tetrodotoxin (TTX) and high external K+ on A and C fibre compound action potential peaks in frog sciatic nerve

Buchanan, S.; Harper, Alexander A.; Elliott, James R.

doi:10.1016/s0304-3940(96)13189-x

Cited by 25 publications

(8 citation statements)

References 8 publications

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“…see Villiere & McLachlan, 1996) but whether TTX‐I channels such as Na V 1.8 are involved in action potential conduction is more controversial. Jeftinija (1994) has presented evidence that suggests that TTX‐I channels are capable of supporting action potential conduction in sensory nerve roots and there is evidence that TTX‐I channels support action potential conduction in amphibian peripheral nerves (Buchanan et al ., 1996; Kobayashi et al ., 1996), rat (Steffens et al ., 2001) and human tissue (Quasthoff et al ., 1995). Certainly, Na V 1.8 mRNA is expressed in the cell bodies of nociceptive somatosensory neurones (Akopian et al ., 1996; Sangameswaran et al ., 1996) and in nodose ganglion neurones (Chen et al ., 1997) and TTX‐I currents (Arbuckle & Docherty, 1995) and TTX‐I somatic action potentials have been described in nociceptive neurones (e.g.…”

Section: Discussionmentioning

confidence: 99%

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials

Farrag

Costa

Docherty

2002

British J Pharmacology

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1 We have studied the eects of prostaglandin E 2 (PGE 2 ) on action potential propagation in the isolated, desheathed vagus and saphenous nerves of rats using an extracellular grease gap recording method. 2 PGE 2 evoked a small depolarization of vagus nerves but had no eect on the stimulation threshold, size or latency of either the A wave (corresponding to conduction in A ®bres) or the C wave (corresponding to conduction in C ®bres) of the compound action potential (CAP) recorded from either vagus or saphenous nerves. 3 Lidocaine (0.01 ± 10 mM) reduced all components of the CAP of both vagus and saphenous nerves. PGE 2 had no signi®cant eect on the sensitivity of any component of the CAP to lidocaine. 4 Tetrodotoxin (TTX, 10 mM) blocked completely both the A wave and the C wave of the CAP in either vagus or saphenous nerves. 5 In saphenous nerve preparations the A wave was blocked by lower concentrations of TTX than the C wave or any component of the CAP in vagus nerve preparations which suggests that somatosensory A ®bres express a dierent sub-type of TTX-sensitive voltage-gated sodium channel (VGSC) than somatosensory C-®bres or visceral sensory ®bres. 6 Chemical activation of VGSCs with veratridine (10 or 50 mM) induced a depolarization in either nerve. The depolarization induced by 50 mM veratridine was blocked by 10 mM TTX. 7 Although TTX-insensitive VGSCs are expressed by some vagal and some somatosensory neurones they do not appear to be expressed functionally in the axons.

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Section: Discussionmentioning

confidence: 99%

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials

Farrag

Costa

Docherty

2002

British J Pharmacology

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“…However, recent studies have suggested the existence of Na + channels resistant to TTX in slow conducting C‐fibres. This has been shown by observing TTX‐resistant (TTX‐R) compound action potentials in frog [5], rabbit [6] and human fibres [7]. TTX‐R Na + currents were also shown in rat primary afferent fibres and play an important role in the conduction of painful stimuli [8,9].…”

Section: Introductionmentioning

confidence: 99%

Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones

Bräu

Elliott

1998

Eur J Anaesthesiol

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Besides the fast tetrodotoxin-sensitive Na+ current, small dorsal root ganglion neurones of rats also possess a slower tetrodotoxin-resistant Na+ current. The blocking effect of commonly used local anaesthetics upon the tetrodotoxin-resistant Na+ current was investigated in the present paper. Dorsal root ganglia were dissected from adult rats and cells were enzymatically isolated. The whole-cell patch clamp technique was then used to measure inward Na+ currents of small dorsal root ganglion neurones. Externally applied local anaesthetics reversibly blocked the tetrodotoxin-resistant Na+ current in a dose-dependent manner. Half-maximal blocking concentrations for tonic block were: lignocaine, 326 microM; prilocaine, 253 microM; mepivacaine, 166 microM; etidocaine, 196 microM bupivacaine, 57 microM procaine, 518 microM benzocaine, 489 microM; tetracaine, 21 microM; and dibucaine, 23 microM. Blocking of the current by lignocaine was independent of temperature. The quaternary lignocaine derivative OX-314 did not have any effect upon the tetrodotoxin-resistant Na+ current when applied externally. High concentrations of tetrodotoxin also blocked the tetrodotoxin-resistant Na+ current with a half-maximal blocking concentration of 115 microM. The block by high tetrodotoxin concentrations did not compete with the lignocaine block, suggesting that there were two independent blocking mechanisms for the two substances. The tetrodotoxin-resistant Na+ currents also showed a marked sensitivity to phasic (use-dependent) block by local anaesthetics.

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“…For amphibians (bullfrog) there was evidence of TTX-resistant Na + channels in peripheral nerve fibres, shown by TTX-resistant C-fibre 1 compound action potentials (CAP) [4,15,16]. Indirect techniques have shown that in mammals these channels are also present in peripheral nerve fibres with C-fibre characteristics [20,24,25].…”

Section: Introductionmentioning

confidence: 99%

Tetrodotoxin block of A-fibre afferents from skin and muscle – a tool to study pure C-fibre effects in the spinal cord

Steffens

Eek

Trudrung

et al. 2003

Pflugers Arch - Eur J Physiol

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The properties of tetrodotoxin (TTX)-resistant C-fibre afferents of the dorsal roots were tested in Sprague-Dawley rats. Dorsal roots (L4-L6) were blocked with TTX (0.5-1 micro M) and the amplitude of the first response of the dorsal horn superficial interneurones (cord dorsum potential, CDP) to electrical stimulation of peripheral C-fibres in combination with natural noxious stimulation was taken as measure for intact conductivity of different kinds of noxious input by means of the C-fibre refractory period. After blockade of dorsal roots with TTX, formerly masked CDPs from muscle C-fibre afferents were uncovered. Noxious pressure to the gastrocnemius soleus muscle belly and noxious pinch to the calcanean tendon proved to be TTX resistant and therefore was propagated centrally. For cutaneous heat nociceptors it could also be shown that conductivity was intact after blockade of the dorsal roots with TTX. However, we could not exclude the TTX resistance of non-nociceptive receptors of muscle or skin. Nevertheless, blockade of afferents with TTX together with suitable stimulation techniques proves to be a reliable method to investigate central effects from C-fibre afferents without contaminating effects from A-fibres in the rat.

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Differential effects of tetrodotoxin (TTX) and high external K+ on A and C fibre compound action potential peaks in frog sciatic nerve

Cited by 25 publications

References 8 publications

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials

Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones

Tetrodotoxin block of A-fibre afferents from skin and muscle – a tool to study pure C-fibre effects in the spinal cord

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Differential effects of tetrodotoxin (TTX) and high external K+ on A and C fibre compound action potential peaks in frog sciatic nerve

Cited by 25 publications

References 8 publications

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E2 on the pharmacology and physiology of propagated action potentials

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E2 on the pharmacology and physiology of propagated action potentials

Local anaesthetic effects on tetrodotoxin-resistant Na+ currents in rat dorsal root ganglion neurones

Tetrodotoxin block of A-fibre afferents from skin and muscle – a tool to study pure C-fibre effects in the spinal cord

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Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials

Differential sensitivity to tetrodotoxin and lack of effect of prostaglandin E₂ on the pharmacology and physiology of propagated action potentials