Nav1.9, G-proteins, and nociceptors

摘要

It is well known that inflammatory mediators, when introduced into peripheral tissues, can trigger pain. This appears to be due, at least in part, to depolarization and increased excitability of nociceptive dorsal root ganglion (DRG) neurons, which innervate peripheral tissues such as the skin (England et al. 1996). Precisely how these changes occur is not yet fully understood. DRG neurons express multiple isoforms of sodium channels, including sodium channel NaT1.9 (Dib-Hajj etal. 1998), which is preferentially expressed in nociceptors (Fang et al. 2002). Nav1.9 exhibits unique electrophysiological and pharmacological properties, including resistance to 250 niu tetrodotoxin (TTX), substantial overlap of activation and steady-state inactivation which bracket resting potential, and very slow activation and inactivation kinetics that enable it to produce a persistent sodium current (Cummins et al. 1999). As a result of these physiological properties, Nav1.9 is not a major contributor to the rapid depolarizing phase of the action potential, but rather contributes to setting the electrogenic properties of nociceptor DRG neurons by modulating their resting potentials and amplifying their responses to subthreshold stimuli (Herzog et al. 2001).