Role of the hyperpolarization-activated current Ih in somatosensory neurons

The hyperpolarization-activated current (I-h) is an inward current activated by hyperpolarization from the resting potential and is an important modulator of action potential firing frequency in many excitable cells. Four hyperpolarization-activated, cyclic nucleotide-modulated subunits, HCN1-4, can form I-h ion channels. In the present study we investigated the function of I-h in primary somatosensory neurons. Neuronal firing in response to current injection was promoted by elevating intracellular cAMP levels and inhibited by blockers of I-h, suggesting that I-h plays a critical role in modulating firing frequency. The properties of I-h in three size classes of sensory neurons were next investigated. In large neurons I-h was fast activating and insensitive to elevations in cAMP, consistent with expression of HCN1. I-h was ablated in most large neurons in HCN1(-/-) mice. In small neurons a slower activating, cAMP-sensitive I-h was observed, as expected for expression of HCN2 and/or HCN4. Consistent with this, I-h in small neurons was unchanged in HCN1(-/-) mice. In a neuropathic pain model HCN1(-/-) mice exhibited substantially less cold allodynia than wild-type littermates, suggesting an important role for HCN1 in neuropathic pain. This work shows that I-h is an important modulator of action potential generation in somatosensory neurons.