Abstract
Mouse B cells express a phosphatidylinositol 4,5-bisphosphate (PIP2)-inhibited large conductance background K channels (LKbg). In inside-out membrane patches, the application of ATP inhibited LKbg due to the generation of PIP2 by PI-kinases. Generation of arachidonic acid (AA) by phospholipase A2 is involved in the apoptosis of immature B cells. The application of AA activated BKbg of B lymphocytes in c-a as well as in i-o patches. The facilitating effects of fatty acids became weaker as the acyl chain is more saturated; AA > oleic acid > plamitic acid. When the activity of BKbg was inhibited by a direct application of PIP2 (5 μM), the addition of AA hardly recovered BKbg activity. The facilitation of BKbg by AA was fully reversible and unaffected by the treatment with inhibitors of various metabolizing enzymes for AA. Consistent with the activation of BKbg, the application of AA induced strong hyperpolarization of membrane potential in WEHI-231 cells. The intracellular [Ca2+] of WEHI-231 was slowly increased by AA, which was partly diminished by KCl-induced membrane depolarization. Besides the increase of BKbg, AA activated Ca2+ permeable nonselective cation channels. In spite of this effect, AA by itself showed a partial inhibitory effect on store-operated Ca2+ entry in WEHI-231. Since the expression of PLA2 is reportedly higher in immature than mature B lymphocytes, the increased driving force for Ca2+ influx by AA might play a crucial role in the regulation and development of B lymphocytes. [J Physiol Sci. 2007;57 Suppl:S246]
