Voltage gated sodium channels and epilepsy

Authors : Simon HEBEISEN

Pages : 780-780

Doi:10.37212/jcnos.610088

View : 12 | Download : 5

Publication Date : 2018-08-18

Article Type : Conference Paper

Abstract :Epilepsy is the fourth most common neurological  disorder and affects people of all ages. Medication for  epilepsy is often life-long and has a major impact on the  quality of life - mostly being related to substantial  adverse effects. Therefore, over 30% of people with  epilepsy do not achieve sufficient seizure control whilst  effective medication being available.  Ion channels are often primary targets of  anticonvulsant drugs. They can either act as blockers for  voltage gated sodium and calcium channels or as  activators for potassium or chloride channels.  Additionally, modulators of ligand gated ion channels  insert ignore into journalissuearticles values(GABA or Glutamate receptors); are frequently used to  treat epilepsy.  Employing a panel of functional  electrophysiological assays using fluorescence based  methods and patch-clamping on a broad range of  voltage and ligand gated ion channels, we were able to  successfully screen for drugs with a beneficial action  profile. In successful leads we found drugs that  selectively interacted with TTX sensitive, neuronal  voltage gated sodium channels. Activation and fast  inactivation were unchanged, while an increased affinity  in the slow inactivated state was observed. This profile  is in contrast to traditional anticonvulsant drugs which  show their major effects on the fast inactivated state of  voltage gated sodium channels. One drug showed  substantial shifts of the voltage dependence of the slow  inactivation only for NaV1.2 and 1.6. This favours this  drug for treating patients with diseases with  compromised NaV1.1 function in interneurons, such as  Alzheimer`s disease.
Keywords : Epilepsy, Voltage gated sodium channels, State dependent inactivation, Patch clamp technique