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Possible role of phosphatidylinositol 4,5, bisphosphate in luteinizing hormone releasing hormone‐mediated M‐current inhibition in bullfrog sympathetic neurons
Author(s) -
Ford Christopher P.,
Stemkowski Patrick L.,
Smith Peter A.
Publication year - 2004
Publication title -
european journal of neuroscience
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.346
H-Index - 206
eISSN - 1460-9568
pISSN - 0953-816X
DOI - 10.1111/j.1460-9568.2004.03786.x
Subject(s) - phosphatidylinositol , endocrinology , medicine , phospholipase c , chemistry , bapta , wortmannin , gonadotropin releasing hormone , receptor , luteinizing hormone , biology , signal transduction , hormone , biochemistry
Luteinizing hormone releasing hormone (LHRH) is a physiological modulator of neuronal excitability in bullfrog sympathetic ganglia (BFSG). Actions of LHRH involve suppression of the noninactivating, voltage‐dependent M‐type K + channel conductance ( g M ). We found, using whole‐cell recordings from these neurons, that LHRH‐induced suppression of g M was attenuated by the phospholipase C (PLC) inhibitor U73122 (10 µ m ) but not by the inactive isomer U73343 (10 µ m ). Buffering internal Ca 2+ to 117 n m with intracellular 20 m m BAPTA + 8 m m Ca 2+ or to < 10 n m with intracellular 20 m m BAPTA + 0.4 m m Ca 2+ did not attenuate LHRH‐induced g M suppression. Suppression of g M by LHRH was not antagonized by the inositol 1,4,5 trisphosphate (InsP 3 ) receptor antagonist heparin (∼ 300 µ m ). Preventing phosphatidylinositol‐4,5‐bisphosphate (PIP 2 ) synthesis by blocking phosphatidylinositol‐4‐kinase with wortmannin (10 µ m ) or with the nonhydrolysable ATP analogue AMP‐PNP (3 m m ) prolonged recovery of LHRH‐induced g M suppression. This effect was not produced by blocking phosphatidyl inositol‐3‐kinase with LY294002 (10 µ m ). Rundown of g M was attenuated when cells were dialysed with 240 µ m di‐octanoyl PIP 2 or 240 µ m di‐octanoyl phosphatidylinositol‐3,4,5‐trisphosphate (PIP 3 ) but not with 240 µ m di‐octanoyl phosphatidylcholine. LHRH‐induced g M suppression was competitively antagonized by dialysis with 240 µ m di‐octanoyl PIP 2 , but not with di‐octanoyl phosphatidylcholine. These results would be expected if LHRH‐induced g M suppression reflects a PLC‐mediated decrease in plasma membrane PIP 2 levels.