TY - JOUR T1 - Role of Tetrodotoxin-Resistant Na<sup>+</sup> Current Slow Inactivation in Adaptation of Action Potential Firing in Small-Diameter Dorsal Root Ganglion Neurons JF - The Journal of Neuroscience JO - J. Neurosci. SP - 10338 LP - 10350 DO - 10.1523/JNEUROSCI.23-32-10338.2003 VL - 23 IS - 32 AU - Nathaniel T. Blair AU - Bruce P. Bean Y1 - 2003/11/12 UR - http://www.jneurosci.org/content/23/32/10338.abstract N2 - When acutely dissociated small-diameter dorsal root ganglion (DRG) neurons were stimulated with repeated current injections or prolonged application of capsaicin, their action potential firing quickly adapted. Because TTX-resistant (TTX-R) sodium current in these presumptive nociceptors generates a large fraction of depolarizing current during the action potential, we examined the possible role of inactivation of TTX-R sodium channels in producing adaptation. Under voltage clamp, TTX-R current elicited by short depolarizations showed strong use dependence at frequencies as low as 1 Hz, although recovery from fast inactivation was complete in ∼10-30 msec. This use-dependent reduction was the result of the entry of TTX-R sodium channels into slow inactivated states. Slow inactivation was more effectively produced by steady depolarization than by cycling channels through open states. Slow inactivation was steeply voltage dependent, with a Boltzmann slope factor of 5 mV, a midpoint near -45 mV (5 sec conditioning pulses), and completeness of ∼93% positive to -20 mV. The time constant for entry (∼200 msec) was independent of voltage from -20 mV to +60 mV, whereas recovery kinetics were moderately voltage dependent (time constant, ∼1.5 sec at -60 mV and ∼0.5 sec at -100 mV). Using a prerecorded current-clamp response to capsaicin as a voltage-clamp command waveform, we found that adaptation of firing occurred with a time course similar to that of development of slow inactivation. Thus, slow inactivation of the TTX-R sodium current limits the duration of small DRG cell firing in response to maintained stimuli and may contribute to cross desensitization between chemical and electrical stimuli. ER -