Expression of Kv4 channels in dorsal root ganglion neurons: Major determinants of the A-type potassium current
The dorsal root ganglion (DRG) contains a heterogeneous population of sensory neurons which include primary nociceptive neurons and the C-fibers implicated in pain signaling. Recent studies have demonstrated DRG neuron hyperexcitability associated with a reduction in the A-type potassium current (IA); however, the molecular identity of the underlying voltage gated potassium (Kv) channels has remained unknown. Kv channels that underlie the somatodendritic A-type current (ISA) in the central nervous system may also underlie the IA in DRG neurons. Patch-clamp electrophysiology, molecular genetics (RT-PCR) and immunohistochemistry were applied to investigate the molecular composition of the IA in acutely dissociated DRG neurons from 7-8 day-old rats. Whole-cell recordings demonstrated a TEA-resistant (20 mM) IA current that is inhibited by 4-aminopyridine (5 mM). Consistent with the presence of Kv4 channel complexes, the midpoint voltages of the activation and steady-state inactivation curves are relatively hyperpolarized and the rate of recovery from inactivation is rapid and voltage dependent. At the whole-tissue and single-cell levels, Kv4.1 mRNA is the predominant Kv4 channel transcript in DRG neurons; and Kv4.1 positive neurons were associated with Nav1.8 mRNA expression, a typical DRG nociceptive marker. Kv4 protein expression was confirmed by immunohistochemistry, which revealed heavy anti-Kv4.1 staining in populations of small neurons. Furthermore, the role of Kv4 channels in DRG neuron excitibility was demonstrated in over- and knock-down expression experiments utilizing Kv4.2-WT and Kv4.2-W362F constructs, respectively. In conclusion, Kv4.1 channels are major determinants of the IA in DRG neurons and play a major role in regulating electrical excitibility resulting from nociceptive stimuli. ^
Biology, Molecular|Biology, Neuroscience|Biology, Cell
Thanawath Ratanadilok Na Phuket,
"Expression of Kv4 channels in dorsal root ganglion neurons: Major determinants of the A-type potassium current"
(January 1, 2008).
ETD Collection for Thomas Jefferson University.