Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein

J. Cheng, A. Nath, B. Knudsen, S. Hochman, J. D. Geiger, M. Ma, D. S.K. Magnuson

Research output: Contribution to journalArticle

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Abstract

Neuronal dysfunction and cell death in patients with human immunodeficiency virus type-I (HIV-1) infection may be mediated by HIV-1 proteins and products released from infected cells. Two HIV-1 proteins, the envelope glycoprotein gp120 and nonstructural protein Tat, are neurotoxic. We have determined the neuroexcitatory properties of HIV-1 tat protein using patch-clamp recording techniques. When fmoles of Tat were applied extracellularly, it elicited dose-dependent depolarizations of human fetal neurons in culture and rat CA1 neurons in slices, both in the absence and presence of tetrodotoxin. These responses were voltage-dependent, reversed at ~0 mV, and were significantly increased by repetitive applications with no evidence of desensitization. That these responses to Tat were due to direct actions on neurons was supported by observations that Tat dose-dependently depolarized outside-out patches excised from cultured human neurons. Removal of extracellular Ca2+ decreased the responses both in neurons and membrane patches. This is the first demonstration that an HIV-1 protein can, in the absence of accessory cells, directly excite neurons and leads us to speculate that Tat may be a causative agent in HIV-1 neurotoxicity.

Original languageEnglish (US)
Pages (from-to)97-106
Number of pages10
JournalNeuroscience
Volume82
Issue number1
DOIs
StatePublished - Sep 25 1997

Fingerprint

tat Gene Products
HIV-1
Neurons
Human Immunodeficiency Virus Proteins
Human Immunodeficiency Virus tat Gene Products
Tetrodotoxin
Patch-Clamp Techniques
HIV Infections
Glycoproteins
Cell Death
HIV
Membranes

Keywords

  • Calcium
  • Depolarization
  • HIV-1
  • Human
  • Neuron
  • Tat

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Cheng, J., Nath, A., Knudsen, B., Hochman, S., Geiger, J. D., Ma, M., & Magnuson, D. S. K. (1997). Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein. Neuroscience, 82(1), 97-106. https://doi.org/10.1016/S0306-4522(97)00174-7

Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein. / Cheng, J.; Nath, A.; Knudsen, B.; Hochman, S.; Geiger, J. D.; Ma, M.; Magnuson, D. S.K.

In: Neuroscience, Vol. 82, No. 1, 25.09.1997, p. 97-106.

Research output: Contribution to journalArticle

Cheng, J, Nath, A, Knudsen, B, Hochman, S, Geiger, JD, Ma, M & Magnuson, DSK 1997, 'Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein', Neuroscience, vol. 82, no. 1, pp. 97-106. https://doi.org/10.1016/S0306-4522(97)00174-7
Cheng, J. ; Nath, A. ; Knudsen, B. ; Hochman, S. ; Geiger, J. D. ; Ma, M. ; Magnuson, D. S.K. / Neuronal excitatory properties of human immunodeficiency virus type 1 Tat protein. In: Neuroscience. 1997 ; Vol. 82, No. 1. pp. 97-106.
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