GTP-induced tetrodotoxin-resistant Na+ current regulates excitability in mouse and rat small diameter sensory neurones

• DOI: 10.1113/jphysiol.2003.039131
• Publication Date: 2003-04-14T23:33:51Z
• Authors: M. D Baker; S. Y Chandra; Y. Ding; S. G Waxman; J. N Wood
• Keywords: Current clamp; Tetrodotoxin; Nociceptor

Peripheral pain thresholds are regulated by the actions of inflammatory mediators. Some act through G-protein-coupled receptors on voltage-gated sodium channels. We have found that a low-threshold, persistent tetrodotoxin-resistant Na+ current, attributed to NaV1.9, is upregulated GTP and its non-hydrolysable analogue GTP-gamma-S, but not GDP. Inclusion GTP-gamma-S (500 microM) in internal solution led an increase maximal current amplitude > 300 % within 5 min. In clamp, upregulation was associated with more negative threshold for action potential induction (by 15-16 mV) assessed from holding -90 mV. This seen neurones without low-threshold or GDP (P < 0.001). addition, depolarized neurones. At -60 mV, generation spontaneous activity initially silent only when upregulated. These findings suggest regulation has important consequences nociceptor excitability.