Discovery of agonist–antagonist pairs for the modulation of Ca [2]+ and voltage-gated K+ channels of large conductance that contain beta1 subunits

Differential Functional Contribution of BK Channel Subunits to Aldosterone-Induced Channel Activation in Vascular Smooth Muscle and Eventual Cerebral Artery Dilation

“…Likewise, in humans admitted with acute ischemic stroke, the median aldosterone serum levels is 0.4 nM [61]. On the other hand, it should be noted that interaction of BK β 1 with µM cholanes [36] led to cholane site identification [16] in this subunit, followed by ligand-base pharmacophore design [3] and identification of nonsteroidal compounds that activated SM BK channels and thus evoked MCA dilation [19], with some activators working at nM [6]. In an analogous route, identification of BK β 1 as a direct aldosterone functional target could lead to novel, more potent compounds of possible use to treat vascular dysfunction and eventual cognitive dysfunction associated with aldosterone actions on the brain vasculature, whether associated with hypertension or not [24,48,56].…”

“…Direct molecular interaction between lipids and ion channel proteins and its contribution to physiology, pathology, and drug development for therapeutics constitutes growing areas of investigation [1][2][3][4][5][6]. In particular, direct ion channel-lipid interactions have been reported to regulate the activity of Ca 2+ /voltage-gated, big conductance K + (BK) channels (reviewed in [7][8][9]).…”