PubMed 17651418

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: KCNQ2 , KCNQ3 , Kir6.2 , Kv7.2 , Kv7.3

Title: K+ M-current regulates the transition to seizures in immature and adult hippocampus.

Authors: Cuie Qiu, Brian N Johnson, Melanie K Tallent

Journal, date & volume: Epilepsia, 2007 Nov , 48, 2047-58

PubMed link:

Loss-of-function mutations in Kv7.2 or Kv7.3 K(+) channel subunits underlies the neonatal epilepsy benign familial neonatal convulsions (BFNC). These two subunits interact to form a functional K(+) channel that underlies the M-current (I(M)), a voltage-dependent noninactivating K(+) current. In BFNC, seizures begin shortly after birth, and spontaneously remit in the first few months of life. The nature of this window of vulnerability is unclear. We address this issue using a hippocampal slice model, to study the effects of I(M) blockade or augmentation on epileptiform activity.We used the Mg(+)(+)-free seizure model in adult and immature (P8-P15) acute rat hippocampal slices. We recorded from both CA1 and CA3 regions using extracellular and intracellular methods.When M-channels are blocked pharmacologically, the transition from interictal to ictal bursting becomes much more likely, especially in immature brain. We also show augmentation of I(M) is effective in stopping ictal events in immature brain, at the developmental age that approximates a human newborn in cortical development. I(M) appears to counter the sustained N-methyl-D-aspartate (NMDA) receptor-mediated depolarizations needed to trigger an ictal event. The increased likelihood of ictal bursting by I(M) blockade is not shared by other selective K(+) channel blockers that increase hippocampal excitability.Voltage-dependent M-channels are activated during interictal bursts and contribute to burst termination. When these channels are compromised, interictal burst duration becomes sufficient to trigger the sustained depolarizations that underlie ictal bursts. This transition to ictal bursts upon I(M) blockade is especially likely to occur in immature hippocampus. This selective function of M-channels likely contributes to the transient window of vulnerability to seizures that occurs with BFNC.