Loss of Dendritic HCN1 Subunits Enhances Cortical Excitability and Epileptogenesis

• DOI: 10.1523/jneurosci.1531-09.2009
• Publication Date: 2009-09-02T17:34:52Z
• Authors: Zhuo Huang; Matthew C. Walker; Mala M. Shah
• Keywords: Hyperpolarization; Pyramidal cell

Hyperpolarization-activated cation nonselective 1 (HCN1) plasticity in entorhinal cortical (EC) and hippocampal pyramidal cell dendrites is a salient feature of temporal lobe epilepsy. However, the significance remains undetermined. We demonstrate that adult HCN1 null mice are more susceptible to kainic acid-induced seizures. After termination these with an anticonvulsant, also developed spontaneous behavioral seizures at significantly rapid rate than their wild-type littermates. This greater seizure susceptibility was accompanied by increased activity −/− EC layer III neurons. Dendritic I h neurons ablated, too. Consequentially, were excitable, despite having hyperpolarized resting membrane potentials (RMPs). In addition, integration EPSPs enhanced considerably such that, normal RMP, 50 Hz train produced action As result this excitability, EPSC frequency onto wild types, causing imbalance between excitatory inhibitory synaptic activity. These results suggest dendritic HCN channels likely play critical role regulating excitability. Furthermore, findings reduction subunit expression during epileptogenesis facilitate disorder.