A-Type Voltage-Gated K⁺ Currents Influence Firing Properties of Isolectin B₄-Positive But Not Isolectin B₄-Negative Primary Sensory Neurons

Abstract

Voltage-gated K+ channels (Kv) in primary sensory neurons are important for regulation of neuronal excitability. The dorsal root ganglion (DRG) neurons are heterogeneous, and the types of native Kv currents in different groups of nociceptive DRG neurons are not fully known. In this study, we determined the difference in the A-type Kv current and its influence on the firing properties between isolectin B4 (IB4)-positive and -negative DRG neurons. Whole cell voltage- and current-clamp recordings were performed on acutely dissociated small DRG neurons of rats. The total Kv current density was significantly higher in IB+-positive than that in IB(4)-negative neurons. Also, 4-aminopyridine (4-AP) produced a significantly greater reduction in Kv currents in IB4-positive than in IB4-negative neurons. In contrast, IB4-negative neurons exhibited a larger proportion of tetraethylammonium-sensitive Kv currents. Furthermore, IB4-positive neurons showed a longer latency of firing and required a significantly larger amount of current injection to evoke action potentials. 4-AP significantly decreased the latency of firing and increased the firing frequency in IB4-positive but not in IB4-negative neurons. Additionally, IB4-positive neurons are immunoreactive to Kv1.4 but not to Kv1.1 and Kv1.2 subunits. Collectively, this study provides new information that 4-AP-sensitive A-type Kv currents are mainly present in IB4-positive DRG neurons and preferentially dampen the initiation of action potentials of this subpopulation of nociceptors. The difference in the density of A-type Kv currents contributes to the distinct electrophysiological properties of IB4-positive and -negative DRG neurons.

Neurokinins enhance excitability in capsaicin-responsive DRG neurons

“…The present knowledge suggests that only a subpopulation of small to medium size IB4 neurons are also sensitive to CAPS and contain neuropeptides SP and CGRP (Chen et al, 1995, Petruska et al, 2003. The neurokinin unresponsive phasic neurons in our study could belong to the population of C-U IB4 positive neurons which are non-peptidergic but respond to 4-AP in a manner similar to those reported by Vydyanathan et al (2005). In our study, >90% of C-R phasic and tonic neurons tested responded to either SP or NKA with an increase in firing in contrast to C-U neurons which did not respond to these agents with an increase in firing.…”

“…The transient K + currents are all sensitive to 4-aminopyridine (4-AP), but only one (Kv1.4, Pongs, 1992,Rasband et al, 2001) is also sensitive to TEA blockade (Gold et al, 1996). Each voltage dependent K + current may contribute differently to the threshold of APs (Vydyanathan et al, 2005), repolarization of the AP as well as after hyperpolarizing potentials, as shown in the present experiments and earlier reports (Sculptoreanu et al, 2005a, Weinreich andWonderlin, 1997).…”

“…Recently, Vydyanathan et al (2005) concluded that 4-AP, which mimicked the effect of SP on firing in our study, increased firing only in IB4 positive neurons, (the majority of which are believed to be capsaicin unresponsive). It was suggested that this was due to selective expression of Kv1.4 channels in these DRG neurons and their inhibition by 4-AP.…”

“…A-type K + currents are important modulators of neuronal firing (Sculptoreanu et al, 2004,Vydyanathan et al, 2005,Yoshimura and de Groat, 1999. A reduction of A-type K + currents has been implicated in the induction of tonic firing in phasic firing DRG neurons, induced by chemical irritation of the bladder (Yoshimura and de Groat, 1999), by gastric ulcers (Dang et al, 2003), following axotomy (Abdulla et al, 2001,Everill and Kocsis, 1999,Yang et al, 2004) and in cats with feline interstitial cystitis (Sculptoreanu et al, 2005a).…”

Morphological and functional diversity of first-order somatosensory neurons

“…As the neuron depolarizes towards threshold, I A activates, thus prolonging the interspike interval. In DRG neurons, K V 1.4 (Rasband et al 2001;Vydyanathan et al 2005), K V 3.4 (Ritter et al 2015), K V 4.1 (Yunoki et al 2014), and K V 4.3 (Yunoki et al 2014;Kuo et al 2017) contribute to I A . Catacuzzeno et al (2008) have shown that 4-aminopyridine eliminated a delay to the first AP in a subtype of tonic neurons.…”