Kalpteki moleküler Ca+2 sinyali üzerinde TRPM katyon kanallarının rolleri

Year 2012, , 83 - 90, 13.07.2012

Mustafa Saygın , Mustafa Nazıroğlu

https://doi.org/10.5835/jecm.omu.29.02.001

Abstract

Transient reseptör potansiyel (TRP) kanalları melastatin (TRPM) kanal ailesi 8 memeli katyon kanalından oluşur ve hemen hemen her dokuda varlığı gösterilmiştir. Kalp ve damar sistemi de dahil olmak üzere tüm TRPM kanalları Ca2+ ve Na+ ’a karşı geçirgendir. Bu nedenle Ca+2 kanalı yerine katyon kanalı denmektedir. Aile üyeleri farklı aktivatörler tarafından etkin hale getirilir. Örnek olarak, TRPM2 katyon kanalları yüksek Ca+2 düzeyi (1μM) ile ilişkili olarak DNA hasarı sonucu ortaya çıkan ADP- riboz (ADPR) ile ya da oksidatif stres modeli hidrojen peroksit (H2 O2) tarafından aktive edilir. TRPM2 kanalları endotel sensörleri olarak da davranır ve kanallar endotelyal bariyer oksidatif stresin neden olduğu disfonksiyondan sorumludur. TRPM4 kardiyak ekstrasistol ve taşikardi gibi aritmilerin oluşumunda rol oynar. TRPM4 ventrikül kası kardiyomyosit hücrelerinde elektriksel potansiyelleri voltaja bağımlı olarak azaltmaktadır. TRPM4 aynı zamanda işlevsel olarak sinoatriyal hücrelerde ifade edilir ve kalp ritminin oluşmasında ve/veya düzensizliğinde anahtar rol oynayabildiği düşünülmektedir. Bu derlemede, deneysel çalışmalarda patch-clamp ve Ca+2 görüntüleme sistemiyle araştırılan antioksidanların inhibitör rolleri de ayrıca özetlenmiştir. Bu derleme çalışmasında sonuç olarak TRPM kanallarının insan kardiyovasküler hastalıklarının tedavisi için önemli yeni farmakolojik hedefler olduğu gözlemlenmiştir. 

Keywords

TRPM katyon kanalları, TRPM2 katyon kanalları, Kalsiyum iyonu, Kalp hücreleri, Kalp-damar hastalıkları, Hücre içine Ca+2 akışı

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