Kalıtımsal Voltaj Kapılı Sodyum Kanalopatileri

Membran potansiyelindeki değişikliklere bağlı olarak açılıp kapanan iyon kanal ailesi grubundan olan voltaj kapılı sodyum kanalları (VKSK), hücre içine seçilimli bir şekilde Na+ iyon geçişini gerçekleştirerek uyarılabilir hücrelerde iletimin ana aktörü olan aksiyon potansiyellerinin oluşum ve yayılımından sorumludurlar. Kanal bu özelliği sebebiyle nöronal uyarım, kas kasılması, nörotransmiter salınımı gibi fizyolojik aktivitelerde oldukça önemli rol oynar. Dolayısıyla VKSK proteinin voltaj-bağımlı kapılanma ve filtre yapısı gibi fonksiyonel özellik gösteren bölgelerinde meydana gelen kalıtımsal mutasyonlar kanalın biyofiziksel özelliklerini değiştirirler ve kanal protein izoformlarının lokalize olduğu bölgeler ile ilişkili olarak merkezi sinir sistemi, periferik sinir sistemi, iskelet-kas sistemi ve kardiyovasküler sistem hastalıklarına yol açabilmektedirler. Bu derlemede, VKSK protein izoformlarında meydana gelen mutasyonlar ve ilişkili hastalıklar belirtilmiş ve ayrıca bu değişikliklerin kanal fonksiyonuna olan etkileri biyofiziksel açıdan detaylıca değerlendirilmiştir. Hastalıklar açısından risk faktörü olan mutasyonların ve bu mutant varyasyonlar sonucunda VKSK’ daki mekanistik değişikliklerin belirtilmesi, hedef odaklı tedavi yöntemlerinin geliştirilmesi ve yeni tedavi metotların oluşturulması bakımından oldukça büyük önem taşımaktadır.

Inherited Voltage Gated Sodıum Channelopathies

Voltage-gated sodium channels (VGSC), one of the members of ion channel family which can open or close due tothe changes in membrane potentials, provide influx of Na+ selectively and this way, they are responsible for initiationand propagation of action potential which is a key element of cellular information in excitable cells. The channel playsan important role in physiological activities such as neuronal stimulation, muscle contraction and neurotransmitterrelease because of its physiological features. Therefore, inherited mutations in functional locations of VGSC proteinsuch as voltage dependent gating and filter structures, change the biophysical properties of the channel and may causediseases at where the channel protein isoforms located such as central nervous system, peripheral nervous system,skeletal muscle system and cardiovascular system. In this review, mutations in VGSC protein isoforms and relateddiseases are defined. Moreover, effects of that changes to the channel function are evaluated biophysically in detail. Itis notably valuable to define mutations which are risk factors for diseases, and also mechanistically changes caused bythose mutant variants in VGSC, in order to develop target-specific treatment and new methods.

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