Persistent (Nav1.9) sodium currents in human dorsal root ganglion neurons.

Abstract

Nav1.9 is of interest to the pain community for a number of reasons, including the human mutations in the gene encoding Nav1.9, SCN11a, that are associated with both pain and loss of pain phenotypes. However, because much of what we know about the biophysical properties of Nav1.9 has been learned through the study of rodent sensory neurons, and there is only 76% identity between human and rodent homologs of SCN11a, there is reason to suggest that there may be differences in the biophysical properties of the channels in human and rodent sensory neurons, and consequently, the contribution of these channels to the control of sensory neuron excitability, if not pain. Thus, the purpose of this study was to characterize Nav1.9 currents in human sensory neurons and compare the properties of these currents with those in rat sensory neurons recorded under identical conditions. Whole-cell patch clamp techniques were used to record Nav1.9 currents in isolated sensory neurons in vitro. Our results indicate that several of the core biophysical properties of the currents, including persistence and a low threshold for activation, are conserved across species. However, we noted a number of potentially important differences between the currents in human and rat sensory neurons including a lower threshold for activation, higher threshold for inactivation, slower deactivation, and faster recovery from slow inactivation. Human Nav1.9 was inhibited by inflammatory mediators, whereas rat Nav1.9 was potentiated. Our results may have implications for the role of Nav1.9 in sensory, if not nociceptive signaling.