Arachidonic acid both inhibits and enhances whole cell calcium currents in rat sympathetic neurons.
We recently reported that arachidonic acid (AA) inhibits L- and N-type Ca(2+) currents at positive test potentials in the presence of the dihydropyridine L-type Ca(2+) channel agonist (+)-202-791 in dissociated neonatal rat superior cervical ganglion neurons [Liu L and Rittenhouse AR. J Physiol (Lond) 525: 291-404, 2000]. In this first of two companion papers, we characterized the mechanism of inhibition by AA at the whole cell level. In the presence of either omega-conotoxin GVIA or nimodipine, AA decreased current amplitude, confirming that L- and N-type currents, respectively, were inhibited. AA-induced inhibition was concentration dependent and reversible with an albumin-containing wash solution, but appears independent of AA metabolism and G protein activity. In characterizing inhibition, an AA-induced enhancement of current amplitude was revealed that occurred primarily at negative test potentials. Cell dialysis with albumin minimized inhibition but had little effect on enhancement, suggesting that AA has distinct sites of action. We examined AA's actions on current kinetics and found that AA increased holding potential-dependent inactivation. AA also enhanced the rate of N-type current activation. These findings indicate that AA causes multiple changes in sympathetic Ca(2+) currents.
Liu
L
L
Program in Neuroscience, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Barrett
C F
CF
Rittenhouse
A R
AR
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology*; D001464:Barium / Q000494:pharmacology; D002121:Calcium Channel Blockers / Q000494:pharmacology*; D020746:Calcium Channels, L-Type / Q000187:drug effects / Q000502:physiology*; D020864:Calcium Channels, N-Type / Q000187:drug effects / Q000502:physiology*; D002478:Cells, Cultured; D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives* / Q000494:pharmacology; D007700:Kinetics; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009474:Neurons / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D009553:Nimodipine / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012710:Serum Albumin, Bovine / Q000494:pharmacology; D017783:Superior Cervical Ganglion / Q000166:cytology / Q000502:physiology; D013779:Tetrodotoxin / Q000494:pharmacology; D013873:Thionucleotides / Q000494:pharmacology; D020866:omega-Conotoxin GVIA / Q000494:pharmacology
D002121:Calcium Channel Blockers; D020746:Calcium Channels, L-Type; D020864:Calcium Channels, N-Type; D013873:Thionucleotides; D006153:Guanosine Diphosphate; D001464:Barium; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D013779:Tetrodotoxin; D009553:Nimodipine; C023427:guanosine 5'-O-(2-thiodiphosphate); D020866:omega-Conotoxin GVIA; D019204:GTP-Binding Proteins