Differential expression of HCN subunits alters voltage-dependent gating of h-channels in CA1 pyramidal neurons from dorsal and ventral hippocampus.

Dougherty KA, Nicholson DA, Diaz L, Buss EW, Neuman KM, Chetkovich DM, Johnston D. Differential expression of HCN subunits alters voltage-dependent gating of h-channels in CA1 pyramidal neurons from dorsal and ventral hippocampus. J Neurophysiol 109: 1940-1953, 2013. First published January 16, 2013; doi:10.1152/jn.00010.2013.-The rodent hippocampus can be divided into dorsal (DHC) and ventral (VHC) domains on the basis of behavioral, anatomical, and biochemical differences. Recently, we reported that CA1 pyramidal neurons from the VHC were intrinsically more excitable than DHC neurons, but the specific ionic conductances contributing to this difference were not determined. Here we investigated the hyperpolarization-activated current (I-h) and the expression of HCN1 and HCN2 channel subunits in CA1 pyramidal neurons from the DHC and VHC. Measurement of I-h with cell-attached patches revealed a significant depolarizing shift in the V-1/2 of activation for dendritic h-channels in VHC neurons (but not DHC neurons), and ultrastructural immunolocalization of HCN1 and HCN2 channels revealed a significantly larger HCN1-to-HCN2 ratio for VHC neurons (but not DHC neurons). These observations suggest that a shift in the expression of HCN1 and HCN2 channels drives functional changes in I-h for VHC neurons (but not DHC neurons) and could thereby significantly alter the capacity for dendritic integration of these neurons.