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

Abstract

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.00010.2013The 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 hyperpolarizationactivated 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. CA1 pyramidal neuron; dorsal hippocampus; ventral hippocampus; hyperpolarization-activated current; HCN channel THE RODENT HIPPOCAMPUS can be divided along its longitudinal (septotemporal) axis into dorsal (the dorsal hippocampus, or DHC) and ventral (the ventral hippocampus, or VHC) components on the basis of behavioral, anatomical, and biochemical differences between these two domains (Bannerman et al.

Alterations in CA1 pyramidal neuronal intrinsic excitability mediated by Ih channel currents in a rat model of amyloid beta pathology

“…These could be due to an increase in the HCN1 channel current as evidenced by voltage clamp recording and a higher level of HCN1 mRNA expression in neurons from Aβ-treated rats. It has been reported that pyramidal neurons with more depolarized membrane potential and higher Rin have a much higher density of Ih channels (Dougherty et al, 2013). On the other hand, as R in inversely correlates with the cell diameter, this change in the passive membrane properties is consistent with a significant reduction in the soma diameters of these neurons in the present model of AD.…”

“…It did not Changes in the intrinsic active membrane properties of pyramidal neurons were further assessed by examining the neuronal responses to depolarizing and hyperpolarizing currents. 16 The sag voltage which reflects the activation of Ih channel was also measured at the soma membrane of CA1 pyramidal neurons in response to hyperpolarizing injected currents (Figs. 4A & B).…”

Functional organization of the hippocampal longitudinal axis

“…The expression profiles of genes encoding adhesion molecules and ion channels 32,43 may determine intrinsic electrophysiological properties of discrete hippocampal neuronal populations, such as the differences in neuronal excitability 45 and synaptic plasticity [46][47] that have been detected along the long axis. For example, hyperpolarisation-activated cation channels HCN1 and HCN2, which mediate hyperpolarization-activated currents (I h ) currents, exhibit dorsoventral expression differences 48 and are important for a spatial function that is dorsoventrally graded [49][50][51] . In general, neurotransmitter receptor expression varies across the long axis for the majority of transmitter systems (Supplementary Table 1).…”

Protein Kinase C Activation Inhibits Rat and Human Hyperpolarization Activated Cyclic Nucleotide Gated Channel (HCN)1 - Mediated Current in Mammalian Cells

“…Such PKC-induced modulation of I h in somatosensory neurons might - if present - link the IFN signaling to neuronal excitability changes [7]. Notably, biophysical characteristics of HCN1 channels expressed in HEK293 cells (in particular their V 1/2 ) are closely related to neuronal HCN channels when recorded at dendrites of pyramidal cortical and hippocampal neurons in cell attached mode [9,27,28]. This apparent phenomenological resemblance might specify HEK293 or N1E-115 cells as model systems to further elucidate neuronal mechanisms of PKC actions.…”