DiBAC4(3) hits a 'sweet spot' for the activation of arterial large-conductance Ca~(2+)-activated potassium channels independently of the beta_1-subunit

摘要

large-conductance Ca~(2+)-activated K+ (BK) channels belong to the family of ion channels with six transmembrane domains per subunit (6TM) and can be activated by both membrane depolarization and increase in intracellular Ca~(2+) (14, 16). In smooth muscle as well as in several other tissues, BK channels are formed by two different types of subunits, termed a- and (3-subunits. The a-subunit contains the pore-forming region, whereas the auxiliary (3-subunit has regulatory functions (15, 21).The smooth muscle beta_1-subunit has been shown to have a crucial role as a molecular tuner for vasoregulation (3, 24). Downregulation of the beta_1-subunit was shown to have a role in a model of acquired hypertension (1) as well as in a model of genetic hypertension (2).