Role of HCN Channels in Neuronal Hyperexcitability after Subarachnoid Hemorrhage in Rats

Abstract

Disruption of ionic homeostasis and neuronal hyperexcitability contribute to early brain injury after subarachnoid hemorrhage (SAH).The hyperpolarization-activated/cyclic nucleotide (HCN)-gated channels play critical role in the regulation of neuronal excitability in hippocampus CA1 region and neocortex, in which the abnormal neuronal activities are more readily provoked. This study was to investigate the interactions between HCN channels and hyperneuronal activity after experimental SAH. The present results from wholecell recordings in rat brain slices indicated that (1)

Potential Implications of HCN Channel Dysfunction after Subarachnoid Hemorrhage

“…First, this ex vivo model builds upon previous in vivo studies (Dreier et al, 2000), which demonstrated that superfusion ofhemoglobinontothecorticalsurface in rats induced CSDs and neuronal death in the presence of high extracellular K ϩ or low glucose. The study by Li et al (2012) is therefore an important addition to the growing body of evidence supporting neuronal hyperexcitability and CSD after SAH. Second, the finding is important because a significant proportion of long-term disability in patients who survive after SAH is related to cognitive impairment.…”

“…In an article recently published in The Journal of Neuroscience, Li et al (2012) examined the contribution of hyperpolarizationactivated cyclic nucleotide-gated (HCN) channels to neuronal hyperexcitability after SAH. The HCN channel family is comprised of four homologous members (HCN1-4) that differ functionally in their current activation kinetics and response to cAMP.…”

“…The HCN channel family is comprised of four homologous members (HCN1-4) that differ functionally in their current activation kinetics and response to cAMP. Li et al (2012) focused on the HCN1 subtype because CSDs are easily provoked in the neocortex and hippocampus, where HCN1 channels are abundant. They performed whole-cell clamp recordings on pyramidal neurons from CA1 in hippocampal slices to examine HCN channel activity, and they mimicked SAH by adding oxyhemoglobin to the perfusate.…”

“…A principal finding of Li et al (2012) was thatinfusionofoxyhemoglobininducedfiring of pyramidal neurons in CA1, and that this neuronal hyperexcitability was mediated by oxyhemoglobin-induced inhibition of HCN channels. These findings are important for several reasons.…”

“…Another pair of important observations by Li et al (2012) are that NO levels alter HCN channel activity and that oxyhemoglobin-induced inhibition of HCN channels might result from scavenging of NO. Li et al (2012) also demonstrated reversal of oxyhemoglobin-induced inhibition of HCN activity and neuronal hyperexcitability by exogenous administration of NO.…”