Journal of the Formosan Medical Association
Volume 108, Issue 9 , Pages 683-693, September 2009

Arsenic Trioxide Modulates the Central Snail Neuron Action Potential

  • Guan-Ling Lu

      Affiliations

    • Department of Pharmacology, College of Medicine, National Taiwan University, Taipei
    • ,
  • Yu-Chi Chang

      Affiliations

    • Department of Pharmacology, College of Medicine, National Taiwan University, Taipei
    • ,
  • Yi-Hung Chen

      Affiliations

    • Graduate Institute of Acupuncture Science, China Medical University, Taichung, Taiwan
    • ,
  • Chia-Ling Tsai

      Affiliations

    • Department of Pharmacology, College of Medicine, National Taiwan University, Taipei
    • ,
  • Ming-Cheng Tsai

      Affiliations

    • Department of Pharmacology, College of Medicine, National Taiwan University, Taipei
    • Corresponding Author InformationCorrespondence to: Professor Ming-Cheng Tsai, Department of Pharmacology, College of Medicine, National Taiwan University, No. 1, Section 1, Jen-Ai Road, Taipei, Taiwan

Received 6 October 2008; received in revised form 16 January 2009; accepted 31 March 2009.

Article Outline

Background/Purpose

The electropharmacological effect of arsenic trioxide (As2O3) is unknown. The present study investigated the effects of As2O3 on spontaneous neuronal impulse activity.

Methods

Intracellular recordings and the two-electrode voltage clamp method were used to study the effect of As2O3 on the RP4 neuron, the number 4 neuron in the right partial ganglion of the giant African snail (Achatina fulica Ferussac).

Results

The RP4 neuron generated spontaneous action potentials, which were affected by As2O3 in a concentration-dependent manner. Extracellular application of 1 or 3 mM As2O3 decreased the frequency of spontaneously generated action potentials. At 10 mM, As2O3 first depolarized and then elicited irreversible bursts of potential (BoPs) at 60 minutes after administration. At 30 mM, As2O3 depolarized the resting membrane potential and abolished the spontaneous action potentials. The BoPs elicited by 10 mM As2O3 were blocked when neurons were pretreated with phospholipase C (PLC) inhibitors (10 mM U73122 or 3 mM neomycin). The BoPs elicited by As2O3 remained unchanged in the presence of KT5720, verapamil, or calcium replacement solution. Voltage-clamp studies revealed that 10 mM As2O3 decreased the fast inward current and had no effect on the steady-state outward current of the neuron.

Conclusion

As2O3 at 10 mM elicits BoPs in central snail neurons and this effect may relate to the PLC activity of the neuron, rather than protein kinase A activity, or calcium influxes of the neuron. As2O3 at higher concentration irreversibly abolishes the spontaneous action potentials of the neuron.

Key Words:  arsenic trioxide , neurons , phospholipase C , second messenger systems , snails

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References 

  1. Hindmarsh JT , McCurdy RF . Clinical and environmental aspects of arsenic toxicity . Crit Rev Clin Lab Sci . 1986;23:315–347
  2. Lu J , Chew EH , Holmgren A . Targeting thioredoxin reductase is a basis for cancer therapy by arsenic trioxide . Proc Natl Acad Sci USA . 2007;104:12288–12293
  3. Vahidnia A , Van der Voet GB , de Wolff FA . Arsenic neurotoxicity—a review . Hum Exp Toxicol . 2007;26:823–832
  4. Ratnaike RN . Acute and chronic arsenic toxicity . Postgrad Med J . 2003;79:391–396
  5. Reichl FX , Szinicz L , Kreppel H , et al.   Effect of glucose in mice after acute experimental poisoning with arsenic trioxide (As2O3) . Arch Toxicol . 1990;64:336–338
  6. Tchounwou PB , Centeno JA , Patlolla AK . Arsenic toxicity, mutagenesis, and carcinogenesis—a health risk assessment and management approach . Mol Cell Biochem . 2004;255:47–55
  7. Nikaido M , Pi J , Kumagai Y , et al.   Decreased enzyme activity of hepatic thioredoxin reductase and glutathione reductase in rabbits by prolonged exposure to inorganic arsenate . Environ Toxicol . 2003;18:306–311
  8. Nolte F , Friedrich O , Rojewski M , et al.   Depolarisation of the plasma membrane in the arsenic trioxide (As2O3)-and anti-CD95-induced apoptosis in myeloid cells . FEBS Lett . 2004;578:85–89
  9. Rojewski MT , Korper S , Thiel E , et al.   Depolarization of mitochondria and activation of caspases are common features of arsenic(III)-induced apoptosis in myelogenic and lymphatic cell lines . Chem Res Toxicol . 2004;17:119–128
  10. Woo SH , Park IC , Park MJ , et al.   Arsenic trioxide induces apoptosis through a reactive oxygen species-dependent pathway and loss of mitochondrial membrane potential in HeLa cells . Int J Oncol . 2002;21:57–63
  11. Ficker E , Kuryshev YA , Dennis AT , et al.   Mechanisms of arsenic-induced prolongation of cardiac repolarization . Mol Pharmacol . 2004;66:33–44
  12. Kuryshev YA , Ficker E , Wang L , et al.   Pentamidine-induced long QT syndrome and block of hERG trafficking . J Pharmacol Exp Ther . 2005;312:316–323
  13. Takeuchi H , Araki Y , Emaduddin M , et al.   Identifiable Achatina giant neurones: their localizations in ganglia, axonal pathways and pharmacological features . Gen Pharmacol . 1996;27:3–32
  14. Kerkut GA , Piggott SM , Walker RJ . The antagonist effect of alpha-amino-pimelic acid on glutamate-induced inhibitions of Helix neurones . Brain Res . 1975;86:139–143
  15. Lin CH , Tsai MC . D-amphetamine-elicited action potential bursts in central snail neurons: role of second messenger systems . J Formos Med Assoc . 2003;102:394–403
  16. Tsai MC , Chen YH , Huang SS . Amphetamine elicited potential changes in vertebrate and invertebrate central neurons . Acta Biol Hung . 2000;51:275–286
  17. Tsai MC , Chen YH . Bursting firing of action potentials in central snail neurons elicited by d-amphetamine: role of the electrogenic sodium pump . Comp Biochem Physiol C Pharmacol Toxicol Endocrinol . 1995;111:131–141
  18. Chen YH , Chang CH , Liang GJ , et al.   Burst firing of action potentials in central snail neurons elicited by d-amphetamine: effect of anticonvulsants . Comp Biochem Physiol C Toxicol Pharmacol . 2000;127:221–231
  19. Chen YH , Tsai MC . Action potential bursts in central snail neurons elicited by d-amphetamine: roles of ionic currents . Neuroscience . 2000;96:237–248
  20. Chen YH , Tsai MC . Bursting firing of action potential in central snail neuron elicited by d-amphetamine: role of the intracellular calcium ions . Comp Biochem Physiol A . 1996;115:195–205
  21. Chen YH , Chow SN , Tsai MC . Ratiometric confocal Ca2+ measurements with visible wavelength indicators in d-amphetamine-treated central snail neuron . Gen Pharmacol . 1998;31:783–788
  22. Chen YH , Tsai MC . Bursting firing of action potentials in central snail neurons elicited by d-amphetamine: role of cytoplasmic second messengers . Neurosci Res . 1997;27:295–304
  23. Lin CH , Tsai MC . The modulation effects of d-amphetamine and procaine on the spontaneously generated action potentials in the central neuron of snail, Achatina fulica Ferussac . Comp Biochem Physiol C Toxicol Pharmacol . 2005;141:58–68
  24. Lin CH , Tsai MC . Effects of procaine on a central neuron of the snail, Achatina fulica Ferussac . Life Sci . 2005;76:1641–1666
  25. Chen YH , Lin CH , Lin PL , et al.   Cocaine elicits action potential bursts in a central snail neuron: the role of delayed rectifying K+ current . Neuroscience . 2006;138:257–280
  26. Tsai MC , Chen YH . (+/−)3,4-Methylenedioxy-amphetamine elicits action potential bursts in a central snail neuron . Exp Neurol . 2007;203:423–444
  27. Lin PL , Lu KL , Lee YL , et al.   Bursts of potential elicited by d-amphetamine in central snail neuron: effect of sodium azide . Basic Clin Pharmacol Toxicol . 2007;101:269–276
  28. Adams DJ , Smith SJ , Thompson SH . Ionic currents in molluscan soma . Annu Rev Neurosci . 1980;3:141–167
  29. Gerr F , Letz R , Ryan PB , et al.   Neurological effects of environmental exposure to arsenic in dust and soil among humans . Neurotoxicology . 2000;21:475–487
  30. Williams SR , Stuart GJ . Mechanisms and consequences of action potential burst firing in rat neocortical pyramidal neurons . J Physiol . 1999;521:467–482
  31. Henkel CC , Asbun J , Ceballos G , et al.   Relationship between extra and intracellular sources of calcium and the contractile effect of thiopental in rat aorta . Can J Physiol Pharmacol . 2001;79:407–414
  32. Florea AM , Splettstoesser F , Busselberg D . Arsenic trioxide (As2O3) induced calcium signals and cytotoxicity in two human cell lines: SY-5Y neuroblastoma and 293 embryonic kidney (HEK) . Toxicol Appl Pharmacol . 2007;220:292–301
  33. Zirpel L , Lippe WR , Rubel EW . Activity-dependent regulation of [Ca2+]i in avian cochlear nucleus neurons: roles of protein kinases A and C and relation to cell death . J Neurophysiol . 1998;79:2288–2302
  34. Ellershaw DC , Greenwood IA , Large WA . Modulation of volume-sensitive chloride current by noradrenaline in rabbit portal vein myocytes . J Physiol . 2002;542:537–547
  35. Arima S , Kohagura K , Xu HL , et al.   Nongenomic vascular action of aldosterone in the glomerular microcirculation . J Am Soc Nephrol . 2003;14:2255–2263
  36. Tsai MC . How messengers modulate the shifting of spontaneously generated action potential into bursts of potentials in central snail neuron? . Acta Biol Hung . 2008;59(Suppl):13–22
  37. Benramdane L , Accominotti M , Fanton L , et al.   Arsenic speciation in human organs following fatal arsenic trioxide poisoning—a case report . Clin Chem . 1999;45:301–306

PII: S0929-6646(09)60391-0

doi:10.1016/S0929-6646(09)60391-0

Journal of the Formosan Medical Association
Volume 108, Issue 9 , Pages 683-693, September 2009

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