[Abstract Title]. - Society for Neuroscience

Support: NIH Grant NS-42150
Erwin Schroedinger Fellowship, Austrian Science Fund
Title: Hyperpolarization-activated current (Ih) contributes to excitability of primary sensory
neurons in rats
Authors: *Q. H. HOGAN, M. POROLI, M. RIGAUD;
Dept Anesthesiol, Med. Coll of WI, Milwaukee, WI
Abstract: In various excitable tissues, the hyperpolarization-activated, cyclic nucleotide-gated
current (Ih) contributes to burst firing by depolarizing the membrane after a period of
hyperpolarization. Alternatively, conductance through open channels Ih channels of the resting
membrane may impede depolarization and excitability. Since primary sensory neurons of the
dorsal root ganglion show both loss of Ih and elevated excitability after peripheral axonal injury
(ref. 1), we examined the contribution of Ih to excitability of these neurons. A sharp electrode
intracellular technique was used to record from neurons in nondissociated ganglia, in order to
avoid potential artefacts due to tissue dissociation and cytosolic dialysis. Ih induced by
hyperpolarizing voltage steps was completely blocked by ZD7288 (approximately 10µM), which
concurrently eliminated the depolarizing sag of transmembrane potential during hyperpolarizing
current injection. Ih was most prominent in rapidly conducting Aα/β neurons, in which ZD7288
produced resting membrane hyperpolarization, slowed conduction velocity, prolonged action
potential (AP) duration, and elevated input resistance. The rheobase current necessary to trigger
an AP was elevated by ZD7288. Of 8 Aα/β neurons that fired repetitively during sustained
depolarization, firing was inhibited by ZD7288 in 7, indicating an excitatory influence of Ih.
Less Ih was evident in more slowly conducting Aδ neurons, resulting in diminished effects of
ZD7288 on AP parameters. Of 6 repetitively firing Aδ neurons, ZD7288 inhibited firing in 5,
and the peak frequency of AP transmission during tetanic bursts was diminished by ZD7288.
Slowly conducting C-type neurons showed minimal Ih, and no effect of ZD7288 on excitability
was seen. After spinal nerve ligation, axotomized neurons had less Ih compared to control
neurons and showed minimal effects of ZD7288 application. We conclude that Ih supports
sensory neuron excitability, and loss of Ih is not a factor contributing to increased neuronal
excitability after peripheral axonal injury.
Reference 1. Anesthesiology 103:360-76, 2005
Disclosures: Q.H. Hogan , None; M. Poroli, None; M. Rigaud, None.
Poster
268. Neuropathic Pain Mechanisms: Ion Channels
Time: Sunday, November 16, 2008, 1:00 pm - 5:00 pm