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Effects of HIV‐1 tat protein on excitability of enteric neurons
Author(s) -
Ngwainmbi Joy,
Smith Tricia H,
Hauser Kurt F,
Dewey William L,
Akbarali Hamid I
Publication year - 2013
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.27.1_supplement.664.5
Subject(s) - patch clamp , motility , neuron , enteric nervous system , activator (genetics) , biology , chemistry , microbiology and biotechnology , medicine , electrophysiology , endocrinology , neuroscience , gene , biochemistry
HIV is mostly transmitted across mucosal surfaces including vaginal, anorectal and oro‐intestinal mucosa. Recent studies demonstrate that HIV infection affects gastrointestinal motility including diarrhea being a serious problem with significant effect on the quality of life. Trans‐activator of transcription (Tat) is an HIV gene that enhances the efficiency of HIV gene transcription. Tat protein together with GP120 has been shown to induce neuronal death, however, its effects on enteric neuronal excitability is not known. In this study we examined the effect of acute (0–30 min) as well as chronic (up to 48 hrs) administration of Tat (1–86) on the electrical activity of mouse enteric neurons in culture. In whole cell patch clamp studies under current clamp, Tat decreased the threshold for action potential generation by 6.8±0.7mV (n=4) within 10 mins of perfusion and increased the number of spikes for each individual neuron. This effect persisted in neurons pretreated with Tat for over 48 hrs (n=15). In some neurons, spontaneous action potentials were observed. The average resting membrane potential of enteric neurons in the presence of Tat was −49mV (n=15) and not significantly different for untreated cells (‐50mV; n= 15). These data suggest that Tat protein has a direct and persistent effect on neuronal excitability. Supported by NIH DA024009