The Role of Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels in the Pathophysiology of Absence Epilepsy

Yavuz M., Onat F.

EPILEPSI, cilt.24, sa.2, ss.41-50, 2018 (ESCI) identifier

  • Yayın Türü: Makale / Derleme
  • Cilt numarası: 24 Sayı: 2
  • Basım Tarihi: 2018
  • Doi Numarası: 10.14744/epilepsi.2018.03371
  • Dergi Adı: EPILEPSI
  • Derginin Tarandığı İndeksler: Emerging Sources Citation Index (ESCI), TR DİZİN (ULAKBİM)
  • Sayfa Sayıları: ss.41-50
  • Anahtar Kelimeler: Absence epilepsy, cyclic adenosine monophosphate, epilepsy, hyperpolarization-activated cyclic nucleotide-gated channels, I(f), I(h), ion channels, rat model, spike-and-wave discharge, SPIKE-WAVE DISCHARGES, HCN CHANNELS, PACEMAKER CHANNELS, I-H, PYRAMIDAL NEURONS, CATION CHANNELS, CAMP SENSITIVITY, SINOATRIAL NODE, DENDRITIC I(H), VOLTAGE-CLAMP
  • Acıbadem Mehmet Ali Aydınlar Üniversitesi Adresli: Hayır

Özet

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels participate in pacemaker currents, modulating the funny current (I[f]) in cardiac cells and the hyperpolarization-activated current (I[h]) in neurons. Depending on the neuronal and synaptic localization, HCN channels regulate synaptic integration, long-term potentiation, synaptic transmission, and resting membrane potential. In summary, it contributes to the electrical activity between the excitatory and inhibitory stimuli through its shunting effect. Several second messengers modulate I(h) currents in the synapses by changing voltage-dependent activation kinetics. I(h) currents are being investigated in numerous central nervous system disorders, including epilepsy. On one hand, it is well known that I(h) currents lead to synchronized oscillations in the rhythmic burst mode in thalamocortical neurons underlying the pathophysiology of absence epilepsy. However, much of the evidence is contradictory. Therefore, it is important to understand the dynamic relationship of HCN channels within the oscillatory networks to determine the regional "queerness" of I(h), and we need further investigation to determine if upregulation or downregulation of I(h) is needed in order to suppress seizure activity.