Tetrodotoxin, Saxitoxin, and Related Substances: Their Applications in Neurobiology

Evans, Martin H.

doi:10.1016/s0074-7742(08)60329-3

Cited by 164 publications

(44 citation statements)

References 280 publications

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“…TTX binds selectively to voltage-activated Na+ channels and in this way blocks the conduction of action potentials (Narahashi et al, 1964;Nakamuraet al, 1965;reviewed in Hille, 1968;Evans, 1972). In the present study, injections of TTX into the perilymph caused a rapid and total elimination of action potentials in the eighth nerve and NM.…”

Section: Methodological Considerationssupporting

confidence: 55%

Afferent influences on brain stem auditory nuclei of the chicken: Neuron number and size following cochlea removal

Born

Rubel

1985

J of Comparative Neurology

228

193

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_Studies of the avian auditory sytem indicate that neurons in nucleus magnocellularis (NM) and nucleus laminaris of young animals are dramatically altered by changes in the auditory receptor. We examined the role of presynaptic activity on these transneuronal regulatory events. TTX was used to block action potentials in the auditory nerve. TTX injections into the perilymph reliably blocked all neuronal activity in the cochlear nerve and NM. Far-field recordings of sound-evoked potentials revealed that responses returned within 6-12 hr after a single TTX injection. Changes in protein synthesis by NM neurons were measured by determining the incorporation of 3H-leucine using autoradiography.NM neurons on the side of the brain ipsilateral to the TTX injection were compared to normally active cells on the other side of the same tissue section.Grain counts over individual neurons revealed that a single injection of TTX produced a 40% decrease in grain density in ipsilateral NM neurons within 1.5 hr after the TTX injection. However, by 24 hr after a single TTX injection, grain densities were not different on the 2 sides of the brain. Continuous activity blockade for 6 hr caused the cessation of amino acid incorporation in a portion of NM neurons and a 15-20% decrease in the remaining neurons. These changes in amino acid incorporation are comparable to those following complete removal of the cochlea (Steward and Rubel, 1965). We also examined NM for neuron loss and soma shrinkage after blocking eighth nerve action potentials.TTX injected every 12 hr for 46 hr caused a 20% neuron loss and an 6% shrinkage of the remaining neurons. Similar reductions were found following cochlea removal (Born and Rubel, 1965). It is concluded that neuronal activity plays a major role in the maintenance of normal NM neurons. Furthermore, these results

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Section: Methodological Considerationssupporting

confidence: 55%

Afferent influences on brain stem auditory nuclei of the chicken: Neuron number and size following cochlea removal

Born

Rubel

1985

J of Comparative Neurology

228

193

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“…Voltage-dependent Nat channels can be specifically blocked by tetrodotoxin (Evans, 1972) while voltage-dependent Ca2+ channels can be blocked by low concentrations of Mn 2 (Hagiwara, 1973 (ScTX) 100 ,ug/ml. at 37 0C.…”

Section: Resultsmentioning

confidence: 99%

Sodium and calcium fluxes in a clonal nerve cell line.

Stallcup¹

1979

The Journal of Physiology

154

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SUMMARY1. 22Na+ and 45Ca2+ fluxes were studied in the clonal nerve cell line PC12. Three distinct types of ion channels were found: (a) voltage-dependent Na+ channels, (b) voltage-dependent Ca2+ channels, and (c) acetylcholine-activated channels permeable to both ions.2. 22Na+ uptake through voltage-dependent Na+ channels is induced by veratridine and scorpion venom, and is inhibited 50 % by 5 x 10-7 M-tetrodotoxin and greater than 98 % by 5 x 106 M-tetrodotoxin.3. o*Ca2+ uptake through voltage-dependent Ca2+ channels is induced by depolarizing the cells in 50 mM-KCl. This flux is not dependent on the presence of Na+ in the medium and is insensitive to 5 x 106 M-tetrodotoxin. However, 1 mM-Mn2+ causes a 95 % inhibition of K+-induced 45Ca2+ uptake.4. Veratridine and scorpion venom also induce voltage-dependent 45Ca2+ uptake which can be blocked by ImM-Mn2+. In contrast to KCl-induced 45Ca2+ uptake, this flux is completely blocked by 5 x 106 M-tetrodotoxin and is abolished by removal of Na+ from the medium. Thus the depolarizing stimulus for Ca2+ uptake in this case is Na+ influx through voltage-dependent Na+ channels.5. Carbamylcholine induces both 22Na+ and 45Ca2+ fluxes which are blocked by nicotinic cholinergic antagonists with the exception of ac-bungarotoxin. The 22Na+ flux occurs exclusively via acetylcholine receptor channels, as evidenced by the lack of effect of 5 x 106 M-tetrodotoxin. In the presence of Na+, almost all of the 45Ca2+ uptake can be blocked by 1mM-Mn2+ and thus occurs via voltage-dependent Ca2+ channels which are activated by the depolarizing Na+ influx. 6-8% of the total 45Ca2+ flux, however, is insenstitive to 1 mM-Mn2+, suggesting that this portion of the uptake occurs via the acetylcholine receptor channels. In Na+-free medium, the Mn2+-resistantf45Ca2+,component increases to 40 % of the total uptake, apparently due to lack of competition from Na+ for the acetylcholine receptor channels. This receptor-linked flux still causes sufficient depolarization to induce the additional 60 % of the Ca2+ flux through voltage-dependent, Mn2+ sensitive Ca2+ channels.6. Mn2+ inhibits Ca2+ flux through voltage-dependent Ca2+ channels by competing for entry through these channels. 50 mM-KCl induces 54Mn2+ fluxes in PC12 cells that are comparable in magnitude to 45Ca2+ fluxes.7. In normal saline 45Ca2+ efflux from PC12 cells is several times more rapid than in Na+-free medium, indicating the presence of a Ca2+-Na+ exchange mechanism.

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“…5 to 10 µg STX eq kg -1 right whale d -1 estimated by Durbin et al (2002) and representing a daily exposure comparable to a lethal oral dose in humans (ca. 7 to 16 µg STX eq kg -1 ; Evans 1972, Schantz et al 1975). It is clearly not possible to directly correlate this exposure rate with toxin levels measured in the right whale feces.…”

Section: Discussionmentioning

confidence: 99%

Paralytic shellfish poisoning (PSP) toxins in North Atlantic right whales Eubalaena glacialis and their zooplankton prey in the Bay of Fundy, Canada

Doucette¹,

Cembella²,

Martin³

et al. 2006

Mar. Ecol. Prog. Ser.

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Tetrodotoxin, Saxitoxin, and Related Substances: Their Applications in Neurobiology

Cited by 164 publications

References 280 publications

Afferent influences on brain stem auditory nuclei of the chicken: Neuron number and size following cochlea removal

Afferent influences on brain stem auditory nuclei of the chicken: Neuron number and size following cochlea removal

Sodium and calcium fluxes in a clonal nerve cell line.

Paralytic shellfish poisoning (PSP) toxins in North Atlantic right whales Eubalaena glacialis and their zooplankton prey in the Bay of Fundy, Canada

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