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 excitability. Since primary sensory neurons of the dorsal root ganglion show both loss of Ih and elevated excitability after peripheral axonal injury, we examined the contribution of Ih to excitability of these neurons. We used a sharp electrode intracellular technique to record from neurons in nondissociated ganglia to avoid potential artefacts due to tissue dissociation and cytosolic dialysis. Neurons were categorized by conduction velocity. Ih induced by hyperpolarizing voltage steps was completely blocked by ZD7288 (approximately 10 μM), 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 and repetitive firing was inhibited by ZD7288, 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. Repetitive firing in these neurons was also inhibited by ZD7288, 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. © 2008 Elsevier B.V. All rights reserved.
Hogan, Q. H., & Poroli, M. (2008). Hyperpolarization-activated current (Ih) contributes to excitability of primary sensory neurons in rats. Brain Research, 1207, 102–110. https://doi.org/10.1016/j.brainres.2008.02.066