Title: Differential distribution and function of hyperpolarization-activated channels in sensory neurons and mechanosensitive fibers.

Authors: Thanh N Doan, Kevin Stephans, Angelina N Ramirez, Patricia A Glazebrook, Michael C Andresen, Diana L Kunze

Journal, date & volume: J. Neurosci., 2004 Mar 31 , 24, 3335-43

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/15056713

Abstract
Sensory neurons express hyperpolarization-activated currents (I(H)) that differ in magnitude and kinetics within the populations. We investigated the structural basis for these differences and explored the functional role of the I(H) channels in sensory neurons isolated from rat nodose ganglia. Immunohistochemical studies demonstrated a differential distribution of hyperpolarization-activated cyclic nucleotide-gated (HCN) protein (HCN1, HCN2, HCN4) in sensory neurons and peripheral terminals. HCN2 and HCN4 immunoreactivity was present in all nodose neurons. In contrast, only 20% of the total population expressed HCN1 immunoreactivity. HCN1 did not colocalize with IB4 (a marker for C-type neurons), and only 15% of HCN1-positive neurons colocalized with immunoreactivity for the vanilloid receptor VR1, another protein associated primarily with C-type neurons. Therefore, most HCN1-containing neurons were A-type neurons. In further support, HCN1 was present in the mechanosensitive terminals of myelinated but not unmyelinated sensory fibers, whereas HCN2 and HCN4 were present in receptor terminals of both myelinated and unmyelinated fibers. In voltage-clamp studies, cell permeant cAMP analogs shifted the activation curve for I(H) to depolarized potentials in C-type neurons but not A-type neurons. In current-clamp recording, CsCl, which inhibits only I(H) in nodose neurons, hyperpolarized the resting membrane potential from -63 +/- 1 to -73 +/- 2 mV and nearly doubled the input resistance from 1.3 to 2.2 GOmega. In addition, action potentials were initiated at lower depolarizing current injections in the presence of CsCl. At the sensory receptor terminal, CsCl decreased the threshold pressure for initiation of mechanoreceptor discharge. Therefore, elimination of the I(H) increases excitability of both the soma and the peripheral sensory terminals.