Arachidonic acid modulates hippocampal calcium current via protein kinase C and oxygen radicals

Neuron. 1990 Oct;5(4):545-53. doi: 10.1016/0896-6273(90)90092-t.

Abstract

Arachidonic acid (AA) is a second messenger liberated via receptor activation of phospholipase A2 or diacylglycerol-lipase. We used whole-cell voltage clamp of acutely isolated hippocampal CA1 pyramidal cells to investigate the hypothesis that AA modulates Ca2+ channel current (ICa) via activation of protein kinase C (PKC) and generation of free radicals. AA depressed ICa in a dose- and time-dependent manner similar to that previously reported for the action of phorbol esters on ICa. A similar depression was seen with a xanthine-based free radical generating system. The specific PKC inhibitor PKCI (19-36), the protein kinase inhibitor H-7, and the superoxide free radical scavenger SOD each blocked ICa depression by 70%-80%. Complete block of the AA response occurred when SOD was used simultaneously with a PKC inhibitor. These data suggest that PKC and free radicals play a role in AA-induced suppression of ICa.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Arachidonic Acid
  • Arachidonic Acids / physiology*
  • Calcium / physiology*
  • Electrophysiology
  • Free Radicals
  • Hippocampus / cytology
  • Hippocampus / physiology*
  • Masoprocol / pharmacology
  • Neurons / physiology
  • Oxygen / physiology*
  • Protein Kinase C / physiology*
  • Superoxide Dismutase / pharmacology

Substances

  • Arachidonic Acids
  • Free Radicals
  • Arachidonic Acid
  • Masoprocol
  • Superoxide Dismutase
  • Protein Kinase C
  • Oxygen
  • Calcium