Arachidonic acid-mediated inhibition of a potassium current in the giant neurons of Aplysia

Miscellaneous · Mon Jan 01 00:00:00 EST 1990

OSTI ID:5475349

Carlson, R O

Biochemical and electrophysiological approaches were used to investigate the role of arachidonic acid (AA) in the modulation of an inwardly rectifying potassium current (I{sub R}) in the giant neurons of the marine snail, Aplysia californica. Using ({sup 3}H)AA as tracer, the intracellular free AA pool in Aplysia ganglia was found to be in a state of constant and rapid turnover through deacylation and reacylation of phospholipid, primarily phosphatidyl-inositol. This constant turnover was accompanied by a constant release of free AA and eicosanoids into the extracellular medium. The effects of three pharmacological agents were characterized with regard to AA metabolism in Aplysia ganglia. 4-O-tetra-decanoylphorbol 13-acetate (TPA), an activator of protein kinase C, stimulated liberation of AA from phospholipid, and 4-bromophenacylbromide (BPB), an inhibitor of phospholipate A{sub 2}, inhibited this liberation. Indomethacin at 250 {mu}M was found to inhibit uptake of AA, likely through inhibition of acyl-CoA synthetase. These agents were also found to modulate I{sub R} in ways which were consistent with their biological effects: TPA inhibited I{sub R}, and both BPB and indomethacin stimulated I{sub R} . Modulation of I{sub R} by these substances was found not to involve cAMP metabolism. Acute application of exogenous AA did not affect I{sub R}; however, I{sub R} in giant neurons was found to be inhibited after dialysis with AA or other unsaturated fatty acids. Also, after perfusion with BSA overnight, a treatment which strips the giant neurons of AA in lipid storage, I{sub R} was found to have increased over 2-fold. This perfusion-induced increase was inhibited by the presence of AA or by pretreatment of the giant neurons with BPB. These results suggest AA, provided through constant turnover from phospholipid, mediates constitutive inhibition of I{sub R}.

• Research Organization: Brandeis Univ., Waltham, MA (United States)
• OSTI ID: 5475349
• Resource Relation: Other Information: Thesis (Ph. D.)
• Country of Publication: United States
• Language: English

Related Subjects

59 BASIC BIOLOGICAL SCIENCES
63 RADIATION, THERMAL, AND OTHER ENVIRON. POLLUTANT EFFECTS ON LIVING ORGS. AND BIOL. MAT.
ARACHIDONIC ACID
METABOLISM
PHORBOL ESTERS
BIOLOGICAL EFFECTS
POTASSIUM
MEMBRANE TRANSPORT
SNAILS
ELECTROPHYSIOLOGY
ACYLATION
ENZYME INHIBITORS
NERVES
PHOSPHOLIPIDS
TRACER TECHNIQUES
TRITIUM COMPOUNDS
ALKALI METALS
ANIMALS
AQUATIC ORGANISMS
CARBOXYLIC ACIDS
CARCINOGENS
CHEMICAL REACTIONS
ELEMENTS
ESTERS
HYDROGEN COMPOUNDS
INVERTEBRATES
ISOTOPE APPLICATIONS
LIPIDS
METALS
MOLLUSCS
MONOCARBOXYLIC ACIDS
NERVOUS SYSTEM
ORGANIC ACIDS
ORGANIC COMPOUNDS
ORGANIC PHOSPHORUS COMPOUNDS
PHYSIOLOGY
550501* - Metabolism- Tracer Techniques
560300 - Chemicals Metabolism & Toxicology