The multiple personalities of h-channels

Abstract

Concepts regarding the function of the hyperpolarization-activated current (Ih) in shaping the excitability of single cells and neuronal ensembles have been evolving rapidly following the recent cloning of genes that encode the underlying 'h-channels' - the HCN genes. This article reviews new information about the transcriptional regulation of these channels, highlighting novel studies that demonstrate short- and long-term modulation of HCN expression, and linking this modulation to mechanisms of neurological diseases.

Figure 1

Pro-excitatory or anti-excitatory? Opposing effects of increased h-channel activity on the modulation of cellular excitability have been suggested. The seemingly opposing actions can be reconciled by considering several factors. These include the spatial distribution and the nature of synaptic inputs and other intrinsic conductances present in the neuron (i.e. the electrophysiological context in which the h-channels operate), as well as the functional properties of the specific h-channel isoforms involved. Traces in the frame on the left are reproduced, with permission, from [16], © (2001) Nature Publishing Group (http://www.nature.com/); traces in the frame on the right are reproduced, with permission, from Ref. [29], © (2002) Nature Publishing Group.