Arachidonic acid reversibly enhances N-type calcium current at an extracellular site.
We examined the effects of arachidonic acid (AA) on whole cell Ca(2+) channel activity in rat superior cervical ganglion neurons. Our companion paper (Liu L, Barrett CF, and Rittenhouse AR. Am J Physiol Cell Physiol 280: C1293-C1305, 2001) demonstrates that AA induces several effects, including enhancement of current amplitude at negative voltages, and increased activation kinetics. This study examines the mechanisms underlying these effects. First, enhancement is rapidly reversible by bath application of BSA. Second, enhancement appears to occur extracellularly, since intracellular albumin was without effect on enhancement, and bath-applied arachidonoyl coenzyme A, an amphiphilic AA analog that cannot cross the cell membrane, mimicked enhancement. In addition, enhancement is voltage dependent, in that currents were enhanced to the greatest degree at -10 mV, whereas virtually no enhancement occurred positive of +30 mV. We also demonstrate that AA-induced increases in activation kinetics are correlated with enhancement of current amplitude. An observed increase in the voltage sensitivity may underlie these effects. Finally, the majority of enhancement is mediated through N-type current, thus providing the first demonstration that this current type can be enhanced by AA.
Barrett
C F
CF
Program in Cellular and Molecular Physiology, University of Massachusetts Medical School, Worcester, Massachusetts 01655, USA.
Liu
L
L
Rittenhouse
A R
AR
D000818:Animals; D000831:Animals, Newborn; D016718:Arachidonic Acid / Q000494:pharmacology*; D002120:Calcium Channel Agonists / Q000494:pharmacology; D002462:Cell Membrane / Q000502:physiology; D002478:Cells, Cultured; 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*; D011758:Pyrroles / 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
D002120:Calcium Channel Agonists; D011758:Pyrroles; D013873:Thionucleotides; C071658:FPL 64176; D006153:Guanosine Diphosphate; D012710:Serum Albumin, Bovine; D016718:Arachidonic Acid; D013779:Tetrodotoxin; C023427:guanosine 5'-O-(2-thiodiphosphate); D020866:omega-Conotoxin GVIA