The hyperpolarization-activated cyclic nucleotide-gated 4 channel as a potential anti-seizure drug target.

ABSTRACT:

Background and purpose

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are encoded by four genes (HCN1-4) with distinct biophysical properties and functions within the brain. HCN4 channels activate slowly at robust hyperpolarizing potentials, making them more likely to be engaged during hyperexcitable neuronal network activity seen during seizures. HCN4 channels are also highly expressed in thalamic nuclei, a brain region implicated in seizure generalization. Here, we assessed the utility of targeting the HCN4 channel as an anti-seizure strategy using pharmacological and genetic approaches.

Experimental approach

The impact of reducing HCN4 channel function on seizure susceptibility and neuronal network excitability was studied using an HCN4 channel preferr

SUBMITTER: Kharouf Q 

PROVIDER: S-EPMC7393203 | biostudies-literature | 2020 Aug

REPOSITORIES: biostudies-literature