Effects of arachidonic acid and the other long-chain fatty acids on the membrane currents in the squid giant axon

Abstract

The effects of arachidonic acid and some other long-chain fatty acids on the ionic currents of the voltage-clamped squid giant axon were investigated using intracellular application of the test substances. The effects of these acids, which are usually insoluble in solution, were examined by using alpha-cyclodextrin as a solvent, alpha-cyclodextrin itself had no effect on the excitable membrane. Arachidonic acid mainly suppresses the Na current but has little effect on the K current. These effects are completely reversed after washing with control solution. The concentration required to suppress the peak inward current by 50% (ED50) was 0.18 mM, which was 10 times larger than that of medium-chain fatty acids like 2-decenoic acid. The Hill number was 1.5 for arachidonic acid, which is almost the same value as for medium-chain fatty acids. This means that the mechanisms of the inhibition are similar in both long- and medium-chain fatty acids. When the long-chain fatty acids were compared, the efficacy of suppression of Na current was about the same value for arachidonic acid, docosatetraenoic acid and docosahexaenoic acid. The suppression effects of linoleic acid and linolenic acid on Na currents were one-third of that of arachidonic acid. Oleic acid had a small suppression effect and stearic acid had almost no effect on the Na current. The currents were fitted to equations similar to those proposed by Hodgkin and Huxley (Hodgkin, A.L., Huxley, A.F. (1952) J. Physiol (London) 117:500-544) and the change in the parameters of these equations in the presence of fatty acids were calculated.(ABSTRACT TRUNCATED AT 250 WORDS)

Structural requirements for charged lipid molecules to directly increase or suppress K+ channel activity in smooth muscle cells. Effects of fatty acids, lysophosphatidate, acyl coenzyme A and sphingosine.

“…The results from the present study are inconsistent with a mechanism involving effects on the bilayer and they tend to support the idea that amphiphiles directly regulate K + channel activity for the following reasons. The notion that "detergent effects" or alterations in "membrane fluidity" (Spector, 1986;Takenaka et al, 1987Takenaka et al, , 1988Bregestovski et al, 1989) underlie the actions of fatty acids and polar lipids is open to question (Carruthers and Melchior, 1988;Cistola, Hamilton, Jackson and Small, 1988). The results from the present study not only fail to support such a mechanism but provide several lines of evidence to the contrary.…”

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

“…A dash denote that the parameter has not been investigated, there is no effect, or that it is not applicable. a, (Takenaka et al, 1987, 1988; Premkumar et al, 1990; Rouzaire-Dubois et al, 1991; Damron et al, 1993; Villarroel, 1993; Chesnoy-Marchais and Fritsch, 1994; Honoré et al, 1994; Lee et al, 1994; Lynch and Voss, 1994; Gubitosi-Klug et al, 1995; Poling et al, 1995; Nagano et al, 1995a; Poling et al, 1996; Soliven and Wang, 1995; Wang and Lu, 1995; Nagano et al, 1997; Garratt et al, 1996; Smirnov and Aaronson, 1996; Villarroel and Schwarz, 1996; Gilbertson et al, 1997; Horimoto et al, 1997; Keros and McBain, 1997; Bogdanov et al, 1998; Bringmann et al, 1998; Devor and Frizzell, 1998; Dryer et al, 1998; Hatton and Peers, 1998; Visentin and Levi, 1998; Bittner and Müller, 1999; Colbert and Pan, 1999; Singleton et al, 1999; Yu et al, 1999; Casavant et al, 2000; Wilson et al, 2000; Holmqvist et al, 2001; Kehl, 2001; McKay and Jennings, 2001; Takahira et al, 2001; Erichsen et al, 2002; Müller and Bittner, 2002; Ramakers and Storm, 2002; Seebungkert and Lynch, 2002; Xiao et al, 2002; Danthi et al, 2003; Ferroni et al, 2003; Judé et al, 2003; Fioretti et al, 2004; Oliver et al, 2004; Sokolowski et al, 2004; Angelova and Müller, 2006, 2009; Feng et al, 2006; Kang et al, 2006; Jacobson et al, 2007; Szekely et al, 2007; Zhao et al, 2007; Börjesson et al, 2008, 2010; Guizy et al, 2008; Xu et al, 2008; Zhang M. et al, 2008; Boland et al, 2009; Koshida et al, 2009; Li et al, 2009; Wang et al, 2009; Decher et al, 2010; Börjesson and Elinder, …”

“…Finally, in 1988, by using α-cyclodextrin to dissolve the fatty acids, this group reported that long-chain PUFAs produced effects similar to medium-chain fatty acids (Takenaka et al, 1988). Intracellularly applied AA (20:4) reversibly suppressed the Na current of the squid giant axon with little effect on the K current.…”

Two novel cardiac atrial K+ channels, IK.AA and IK.PC.

“…Indirect, but potentially physiologically relevant, modulation of ion channels through an alteration of membrane composition has been proposed. This membrane destabilization is a possible mechanism of fatty acids in modifying the activity of squid giant axon Na ÷ (Takenaka, Horie, Hori, and Kawakami, 1988) and aortic smooth muscle K ÷ channels (Bregestovski, Bolotina, and Serebryakov, 1989). An important caveat is the possibility of a detergent effect of lipophilic compounds at concentrations close to the critical miceUar concentration, where aggregates of monomers disrupt membranes and can apparently create lipidic pores (Sawyer and Anderson, 1989).…”