Abstract
Studies of pathological ion channel regulation as an underlying mechanism of epilepsy have revealed alterations in the h-current in several animal models. While earlier reports indicate that downregulation of the h-current is pro-excitatory on the single neuron level, we found an upregulation of Ih in hyperexcitable CA1 pyramidal neuron dendrites following experimental febrile seizures. In addition, in several CA1 pyramidal neuron computational models of different complexity, h-current upregulation has been shown to lead to pro-excitable effects. This focused review examines the complex impact of altered h-current on neuronal resting membrane potential (RMP) and input resistance (Rin), as well as reported interactions with other ionic conductances.
Highlights
The study of channelopathies, pathological changes in the expression and function of ion channels, has gained momentum in recent years in epilepsy research – several idiopathic epilepsies have been linked to underlying mutations in channel encoding genes
While earlier reports indicate that downregulation of the h-current is pro-excitatory on the single neuron level, we found an upregulation of Ih in hyperexcitable CA1 pyramidal neuron dendrites following experimental febrile seizures
The decreased mobility resulted from a >2-fold increase in the fraction of surface expressed HCNchannel proteins (Noam et al, 2008). These results indicate the potential for rapid activity-dependent regulation of Ih by fast removal or insertion of existing hyperpolarization-activated cation (HCN) channel proteins
Summary
The study of channelopathies, pathological changes in the expression and function of ion channels, has gained momentum in recent years in epilepsy research – several idiopathic epilepsies (inherited) have been linked to underlying mutations in channel encoding genes (for reviews see, Catterall et al, 2008; Hirose et al, 2005; Lerche et al, 2005; Mulley et al, 2003). This focused review examines the complex impact of altered h-current on neuronal resting membrane potential (RMP) and input resistance (Rin), as well as reported interactions with other ionic conductances.
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