Fatty acids directly increase the activity of Ca(2+)-activated K+ channels in rabbit coronary smooth muscle cells

Abstract

The large conductance Ca2+ activated K+ channel (BK channel) has been considered to play an important role in the excitability and contractility of vascular smooth muscle cells. Activation of the BK channel causes the hyperpolarization and relaxation of vascular smooth muscle cells. It has been reported that fatty acids can affect the BK channel activity and its concentration is increased significantly during myocardial ischemia. These reports suggest that fatty acids may contribute to the ischemic coronary vasodilation by increasing the BK channel activity. However, the underlying mechanism of fatty acid-induced activation of the BK channel is still uncertain. In the present study, we measured the effect of fatty acids on the BK channel activity in rabbit coronary smooth muscle cells by using patch clamp method and also examined its underlying mechanism. Arachidonic acid (AA) dissolved in DMSO activated the BK channel in a dose-dependent manner (from 0.5 to 10 microM), and DMSO (0.1%) alone had no effect on the activity of the BK channel. Arachidonic acid activated BK channels in both cell-attached and inside-out patches, but the onset and recovery of this effect were slower in the cell-attached patch configuration. The BK channel activity was also increased by other fatty acids, including myristic acid, linoleic acid, palmitoleic acid and palmitic acid. Long chain fatty acids were more effective than short chain fatty acids (myristic acid), and there was no statistical difference between the effect of saturated (palmitic acid) and unsaturated fatty acids (palmitoleic acid) on the BK channel activity. The concentration of Ca2+ and Mg2+ in the bathing solution had no appreciable effects on the AA-induced increase of BK channel activity. From the above results, it may be concluded that fatty acids directly increase the BK channel activity and may contribute to the ischemic coronary vasodilatation in rabbit coronary smooth muscle cells.

Actions and Mechanisms of Polyunsaturated Fatty Acids on Voltage-Gated Ion Channels

“…c, (Schledermann et al, 2001; Liu and Wu, 2003; Wang et al, 2004; Guizy et al, 2005; Gavrilova-Ruch et al, 2007). d, (Bregestovski et al, 1989; Kirber et al, 1992; Ling et al, 1992; Ahn et al, 1994; Duerson et al, 1996; Zou et al, 1996; Twitchell et al, 1997; Devor and Frizzell, 1998; Stockand et al, 1998; Denson et al, 1999, 2000, 2005, 2006; Barlow et al, 2000; Wu et al, 2000; Fukao et al, 2001; Lu et al, 2001, 2005; Zhang et al, 2001; Zhang P. et al, 2008; Clarke et al, 2002, 2003; Lauterbach et al, 2002; Li et al, 2002, 2010; Ye et al, 2002; Hamilton et al, 2003; Gauthier et al, 2004, 2014; Zheng et al, 2005, 2008; Yang M. et al, 2005; Sun et al, 2007, 2009; Morin et al, 2007a,b,c; Gebremedhin et al, 2008; Godlewski et al, 2009; Lai et al, 2009; Wang et al, 2011a,b; Enyeart and Enyeart, 2013; Harris et al, 2013; Latorre and Contreras, 2013; Hoshi et al, 2013a,b,c,d; Kacik et al, 2014; Martín et al, 2014; Olszewska et al, 2014; Yan et al, 2014). e, (Chyb et al, 1999; Watanabe et al, 2003; Kahn-Kirby et al, 2004; Hu et al, 2006; Jörs et al, 2006; Oike et al, 2006; Reiter et al, 2006; Andersson et al, 2007; Hartmannsgruber et al, 2007; Matta et al, 2007; Vriens et al, 2007; Rock et al, 2008; Delgado and Bacigalupo, 2009; Shimizu et al, 2009; Parnas et al, 2009a,b; Zhang et al,...…”

Modulation of BKCaChannel Gating by Endogenous Signaling Molecules

“…Once released, arachidonic acid as well as its metabolites such as hydroxyeicosatetraenoic acids (HETEs), epoxyeicosatrienoic acid (EET), dihydroxyeicosatrienoic acids (DHETs), exert a variety of effects (93, 97), including stimulation of BK Ca channels in pituitary tumor cells (32, 127), artery smooth muscle cells (3, 6, 29, 46, 63), and heterologous expression systems (39, 42). The stimulatory action of various fatty acids on the BK Ca channels has been typically attributed to an increase in P o (3, 29, 32) and/or to an increase in N (3). How the changes in P o correlate with the changes in the functional domains of the channel, the gate, the VSDs and the gating ring, have not been fully explored.…”

Lipid regulation of BK channel function

“…Increase in BK channel activity by low μM FA has been reported in VSM (Kirber et al, 1992; Ahn et al, 1994; Dopico et al, 1994; Clarke et al, 2002, 2003; Martín et al, 2013) and GH3 cells (Denson et al, 2000), and following channel expression in HEK293 cells (Hoshi et al, 2013a-c) and Xenopus oocytes (Sun et al, 2007). FA-induced BK activation occurs at a wide range of [Ca 2+ ] i , and [Mg 2+ ] i (Ahn et al, 1994), and in virtual absence of Ca 2+ i (Clarke et al, 2002; Hoshi et al, 2013b).…”

“…FA-induced BK activation occurs at a wide range of [Ca 2+ ] i , and [Mg 2+ ] i (Ahn et al, 1994), and in virtual absence of Ca 2+ i (Clarke et al, 2002; Hoshi et al, 2013b). Moreover, FAs neither require voltage-sensor activation (Hoshi et al, 2013b) nor alter the slope of the activity-voltage relationship (Denson et al, 2000).…”

“…Cis-unsaturated FAs increase GH3 cell BK current whereas saturated or trans -unsaturated FAs have no effect (Denson et al, 2000). On the other hand, long-chain FAs are more effective than short-chain counterparts in activating VSM BK channels (Ahn et al, 1994; Clarke et al, 2002). The mechanisms and targets underlying differential modulation of BK currents by FA of variant structure remain unidentified.…”