Ca2+-dependent K+ channels in bovine adrenal chromaffin cells are modulated by lipoxygenase metabolites of arachidonic acid.
Fatty acids play an important role in a variety of physiological processes including ion channel modulation and catecholamine release. Using patch-clamp techniques we show that arachidonic acid (AA) is converted to lipoxygenase metabolites (LOMs) to potentiate activity of the Ca2+ and voltage-dependent, large-conductance K+ channel (BK) in bovine adrenal medullary chromaffin cells (BAMCCs). AA and LOM potentiation of BK current and recovery from potentiation were unaffected by the nonhydrolyzable ATP analogue AMP-PNP, or by exclusion of nucleotides in excised patch recordings. Also, AA and LOM potentiation of BK channel activity in outside-out patches exposed to strong Ca2+ buffering ruled out cytoplasmic messengers or changes in intracellular Ca2+ levels as causative factors. Lipoxygenase inhibitor attenuated AA, but not LOM potentiation of BK activity in outside-out patches, indicating that lipoxygenase processing of AA is possible in excised membrane patches, possibly via a membrane associated lipoxygenase. AA and LOM release have been implicated in the mechanics of catecholamine secretion from BAMCCs. By limiting action potential duration and thus voltage-gated Ca2+ influx, fatty acid potentiation of BK current may serve an inhibitory feedback function in regulating secretion from BAMCCs.
Twitchell
W A
WA
Department of Biological Sciences, Purdue University, West Lafayette, IN 47907, USA.
Peña
T L
TL
Rane
S G
SG
D000255:Adenosine Triphosphate / Q000494:pharmacology; D000313:Adrenal Medulla / Q000166:cytology*; D000818:Animals; D001095:Arachidonic Acids / Q000378:metabolism*; D002118:Calcium / Q000494:pharmacology*; D002417:Cattle; D002478:Cells, Cultured; D019439:Chromaffin Cells / Q000737:chemistry*; D004357:Drug Synergism; D006160:Guanosine Triphosphate / Q000494:pharmacology; D015289:Leukotrienes / Q000494:pharmacology; D008084:Lipoxygenase / Q000378:metabolism*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*
D001095:Arachidonic Acids; D015289:Leukotrienes; D015221:Potassium Channels; C025348:arachidonic acid 5-hydroperoxide; D006160:Guanosine Triphosphate; D000255:Adenosine Triphosphate; D008084:Lipoxygenase; D002118:Calcium