EXPRESSION PATTERN OF BK CHANNELS ON VARIOUS OXIDATIVE STRESS CONDITIONS IN SKELETAL MUSCLE

Abstract

BK (large conductance Ca2+-activated potassium) channels are expressed in myocytes though changes in their molecular levels in the presence of oxidative stress is not clear, yet. Excessive production of reactive oxygen species leads to many diseases including periodic paralysis. Therefore, determination the molecular effects of various oxidative stress conditions may reveal the possible mechanism and potential therapeutic effects. In the present study, isolated rat soleus muscle where KCNMA1 genes encoding BK channel protein expressed widely in skeletal muscle, were exposed to cyclopiazonic acid (CPA) and also hydrogen peroxide (H2O2) as oxidative stress inducers. Streptozotocin-induced diabetes mellitus model was also used to demonstrate the effects of the endogenous source of oxidative stress. Moreover, NS1619, a BK channel opener was used whether the activation of the channel re-regulate the channel expression back. After the incubation periods, KCNMA1 gene expression levels of each groups were determined by real-time PCR experiments. While CPA and H2O2 decreased the KCNMA1 expression significantly, its expression did not change in systemic diabetes mellitus condition. However, the transcriptional level significantly decreased in diabetes in the presence of H2O2. On the other hand, KCNMA1 expression was re-regulated back to the control’s level by addition of NS1619 in solely hydrogen peroxide groups. The results demonstrated for the first time that acute oxidative stress, rather than systemic conditions, effects the KCNMA1 gene expression level in skeletal muscle. The study was also showed the effects of NS1619 on the regulation of transcriptional levels of BK channel protein in hydrogen peroxide conditions.