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Nrf2 Deletion is Associated with Impaired BK Ca Channel Expression and Function in Rat Cerebral Arterial Muscle Cells
Author(s) -
Gebremedhin Debebe,
Harder David Rae,
Lombard Julian H.
Publication year - 2018
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2018.32.1_supplement.575.7
Subject(s) - bk channel , chemistry , protein subunit , cerebral arteries , knockout mouse , medicine , endocrinology , potassium channel , anatomy , biology , biochemistry , gene
The BK Ca channel is ubiquitous in cerebral arterial muscle cells and other brain cell types and regulates cell excitability by sensing and reacting to changes in [Ca 2+ ]. The BK Ca channels are formed by tetramers of the pore‐forming α‐subunit and the accessary β1 subunit. The accessary β1 subunit unit is the sensor for changes in Ca 2+ and voltage to regulate BK Ca channel function. The BK Ca channel is one of the downstream targets regulated by Nrf2 antioxidant defenses. We investigated the influence of deletion of Nrf2 on the expression and activities of BK Ca single‐channel current in cerebral arterial muscle cells of Nrf2 wild type and knockout rats. In this study we found that the openings of a large conductance BK Ca single‐channel current was markedly reduced in cerebral arterial muscle cells of Nrf2 knockout rats compared to those recorded from Nrf2 wild type rat cerebral arterial muscle cells at the same patch potential and symmetrical KCl (145 mM) recording solution. Nrf2 knockout also resulted in reduced expression of the proteins for both the pore forming BK Ca channel α‐subunit and the accessary BK Ca channel β‐subunit in rat cerebral arteries compared to cerebral arteries of Nrf2 wild type rats. Furthermore, knockout of Nrf2 significantly attenuated the ability of the Nrf2 activator sulforaphane (3 μM) to increase the openings of the BK Ca single‐channel currents recorded from cell‐attached patches of Nrf2 knockout rat cerebral arterial muscle cells at a patch potential of 40 mV compared to those measured in Nrf2 wild type cerebral arterial muscle cells. These findings suggest that Nrf2 antioxidant defenses regulate BK Ca channel expression and activity in rat cerebral arterial muscle cells and may influence the dynamics of the cerebral circulation under normal or oxidative stress conditions. Support or Funding Information NIH #R01‐HL128242 and # R21‐OD018309) and NIH RO1 HL0338833. This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .