Expression and function of a CP339,818-sensitive K⁺ current in a subpopulation of putative nociceptive neurons from adult mouse trigeminal ganglia

Trigeminal ganglion (TG) neurons are functionally and morphologically heterogeneous, and the molecular basis of this heterogeneity is still not fully understood. Here we describe experiments showing that a subpopulation of neurons expresses a delayed-rectifying K⁺ current (I_DRK) with a characteristically high (nanomolar) sensitivity to the dihydroquinoline CP339,818 (CP). Although submicromolar CP has previously been shown to selectively block Kv1.3 and Kv1.4 channels, the CP-sensitive I_DRK found in TG neurons could not be associated with either of these two K⁺ channels. It could neither be associated with Kv2.1 channels homomeric or heteromerically associated with the Kv9.2, Kv9.3, or Kv6.4 subunits, whose block by CP, tested using two-electrode voltage-clamp recordings from Xenopus oocytes, resulted in the low micromolar range, nor to the Kv7 subfamily, given the lack of blocking efficacy of 3 µM XE991. Within the group of multiple-firing neurons considered in this study, the CP-sensitive I_DRK was preferentially expressed in a subpopulation showing several nociceptive markers, such as small membrane capacitance, sensitivity to capsaicin, and slow afterhyperpolarization (AHP); in these neurons the CP-sensitive I_DRK controls the membrane resting potential, the firing frequency, and the AHP duration. A biophysical study of the CP-sensitive I_DRK indicated the presence of two kinetically distinct components: a fast deactivating component having a relatively depolarized steady-state inactivation (I_DRKf) and a slow deactivating component with a more hyperpolarized V_1/2 for steady-state inactivation (I_DRKs).