Lipid regulation of BK channel function

Abstract

This mini-review focuses on lipid modulation of BK (MaxiK, BKCa) current by a direct interaction between lipid and the BK subunits and/or their immediate lipid environment. Direct lipid-BK protein interactions have been proposed for fatty and epoxyeicosatrienoic acids, phosphoinositides and cholesterol, evidence for such action being less clear for other lipids. BK α (slo1) subunits are sufficient to support current perturbation by fatty and epoxyeicosatrienoic acids, glycerophospholipids and cholesterol, while distinct BK β subunits seem necessary for current modulation by most steroids. Subunit domains or amino acids that participate in lipid action have been identified in a few cases: hslo1 Y318, cerebral artery smooth muscle (cbv1) R334,K335,K336, cbv1 seven cytosolic CRAC domains, slo1 STREX and β1 T169,L172,L173 for docosahexaenoic acid, PIP2, cholesterol, sulfatides, and cholane steroids, respectively. Whether these protein motifs directly bind lipids or rather transmit the energy of lipid binding to other areas and trigger protein conformation change remains unresolved. The impact of direct lipid-BK interaction on physiology is briefly discussed.

The urothelium of a hibernator: the American black bear

“…; Ulluwishewa et al. ), membrane solute transporters (Ma and Eaton ; Dopico and Bukiya ), and even endocytic vessel formation and permeability (Grasso and Calderon , ). For hibernating bears dietary fat has special importance and significance.…”

“…Importantly in many mammalian species, dietary lipids have been shown to profoundly affect both membrane lipid composition and membrane function (including membrane permeability, activity of membrane – bound enzymes and receptors, and endocytosis and exocytosis (Abeywardena et al. ; Awad ; Dopico and Bukiya ; Spector and Yorek ; reviewed in Kummerow and Grasso and Calderon ), as well as tight junction permeability and occludin expression (Jiang et al. ).…”

Statin therapy exacerbates alcohol-induced constriction of cerebral arteries via modulation of ethanol-induced BK channel inhibition in vascular smooth muscle

“…Cholesterol (CLR) is one of the major structural lipid components of animal cell membranes, a key mediator in lipid homeostasis, and precursor for the biosynthesis of steroid hormones, bile acids and vitamin D [26,17,22]. However, high levels of CLR in humans represent a risk factor for life-threatening cardio/cerebrovascular conditions, including heart attack and stroke [30].…”

Activation of Calcium- and Voltage-gated Potassium Channels of Large Conductance by Leukotriene B4

“…In this work, we demonstrated that this site can also accommodate LTB4. Therefore, two endogenous lipids from different chemical groups (heterocyclic cholane steroids and linear leukotrienes) can share their site of action on an ion channel protein, an unusual phenomenon because lipid-sensing sites on ion channels, BK in particular, do not share ligands from different lipid species (1,43). The physiological implications of such overlap remain to be explored.…”