Impairment of brain mitochondrial charybdotoxin- and ATP-insensitive BK channel activities in diabetes.

E Noursadeghi, A Jafari, R Saghiri, R Sauve, A Eliassi

Neuromolecular medicine 2014 Dec

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Existing evidence indicates an impairment of mitochondrial functions and alterations in potassium channel activities in diabetes. Because mitochondrial potassium channels have been involved in several mitochondrial functions including cytoprotection, apoptosis and calcium homeostasis, a study was carried out to consider whether the gating behavior of the mitochondrial ATP- and ChTx-insensitive Ca(2+)-activated potassium channel (mitoBKCa) is altered in a streptozotocin (STZ) model of diabetes. Using ion channel incorporation of brain mitochondrial inner membrane into the bilayer lipid membrane, we provide in this work evidence for modifications of the mitoBKCa ion permeation properties with channels from vesicles preparations coming from diabetic rats characterized by a significant decrease in conductance. More importantly, the open probability of channels from diabetic rats was reduced 1.5-2.5 fold compared to control, the most significant decrease being observed at depolarizing potentials. Because BKCa β4 subunit has been documented to left shift the BKCa channel voltage dependence curve in high Ca(2+) conditions, a Western blot analysis was undertaken where the expression of mitoBKCa α and β4 subunits was estimated using of anti-α and β4 subunit antibodies. Our results indicated a significant decrease in mitoBKCa β4 subunit expression coupled to a decrease in the expression of α subunit, an observation compatible with the observed decrease in Ca(2+) sensitivity. Our results thus demonstrate a modification in the mitoBKCa channel gating properties in membrane preparations coming from STZ model of diabetic rats, an effect potentially linked to a change in mitoBKCa β4 and α subunits expression and/or to an increase in reactive oxygen species production in high glucose conditions.

Citation

E Noursadeghi, A Jafari, R Saghiri, R Sauve, A Eliassi. Impairment of brain mitochondrial charybdotoxin- and ATP-insensitive BK channel activities in diabetes. Neuromolecular medicine. 2014 Dec;16(4):862-71