2.8.3. K*V*1.4, K*V*3.4 and K*V*4 Channels

The K*<sup>V</sup>* channels K*V*1.4, K*V*3.4 and K*V*4 members contribute to the so-called transient A-current (I*A*) [242,243], which plays a key role in regulating AP firing in DRG neurons [210,244]. The somata, axons and central terminals of DRG neurons that abut the spinal dorsal horn are enriched with K*V*3.4 channels. The expression of K*V*4.3 channels, on the other hand is restricted to the somata of

non-peptidergic DRG neurons [245]. The rapidly inactivating K*V*3.4 channel is a key player in AP repolarization in DRG neurons [246,247]. Activating PKC through physiological or pharmacological means leads to a decline in fast N-type inactivation in endogenously expressed K*V*3.4 channels. This directly impacts the biophysical properties of the nociceptor: the AP gets narrowed while the AP repolarization is accelerated [248]. Specific siRNAs that selectively target K*V*3.4 channel expression abolish the changes in AP waveform mediated by PKC activation [248]. In a rat model of cervical spinal cord injury (SCI), the surface expression of K*V*3.4 channels was shown to be impaired; such dysregulation was associated with the failure of PKC to shorten the AP duration in DRG neurons [249]. Similarly, the phosphatase calcineurin (CaN) antagonizes PKC activity as revealed by a reduction in the inactivation of K*V*3.4 channels upon pharmacological inhibition of the former [250].
