TY - JOUR T1 - Sodium Channel β2 Subunits Regulate Tetrodotoxin-Sensitive Sodium Channels in Small Dorsal Root Ganglion Neurons and Modulate the Response to Pain JF - The Journal of Neuroscience JO - J. Neurosci. SP - 7984 LP - 7994 DO - 10.1523/JNEUROSCI.2211-06.2006 VL - 26 IS - 30 AU - Luis F. Lopez-Santiago AU - Marie Pertin AU - Xavier Morisod AU - Chunling Chen AU - Shuangsong Hong AU - John Wiley AU - Isabelle Decosterd AU - Lori L. Isom Y1 - 2006/07/26 UR - http://www.jneurosci.org/content/26/30/7984.abstract N2 - Voltage-gated sodium channel (Nav1) β2 subunits modulate channel gating, assembly, and cell-surface expression in CNS neurons in vitro and in vivo. β2 expression increases in sensory neurons after nerve injury, and development of mechanical allodynia in the spared nerve injury model is attenuated in β2-null mice. Thus, we hypothesized that β2 modulates electrical excitability in dorsal root ganglion (DRG) neurons in vivo. We compared sodium currents (INa) in small DRG neurons from β2+/+ and β2−/− mice to determine the effects of β2 on tetrodotoxin-sensitive (TTX-S) and tetrodotoxin-resistant (TTX-R) Nav1 in vivo. Small-fast DRG neurons acutely isolated from β2−/− mice showed significant decreases in TTX-S INa compared with β2+/+ neurons. This decrease included a 51% reduction in maximal sodium conductance with no detectable changes in the voltage dependence of activation or inactivation. TTX-S, but not TTX-R, INa activation and inactivation kinetics in these cells were slower in β2−/− mice compared with controls. The selective regulation of TTX-S INa was supported by reductions in transcript and protein levels of TTX-S Nav1s, particularly Nav1.7. Low-threshold mechanical sensitivity was preserved in β2−/− mice, but they were more sensitive to noxious thermal stimuli than wild type whereas their response during the late phase of the formalin test was attenuated. Our results suggest that β2 modulates TTX-S Nav1 mRNA and protein expression resulting in increased TTX-S INa and increases the rates of TTX-S Nav1 activation and inactivation in small-fast DRG neurons in vivo. TTX-R INa were not significantly modulated by β2. ER -