Various neurotransmitters excite neurons by suppressing a ubiquitous, voltage-dependent, noninactivating K+ conductance called the M-conductance (gM). In bullfrog sympathetic ganglion neurons the suppression of gM by the P2Y agonist @entity855 involves phospholipase C (PLC). The present results are consistent with the involvement of the lipid and @entity19260 cycles in the effects of both P2Y and muscarinic cholinergic agonists on gM. Impairment of resynthesis of @entity1078 (PIP2) with the @entity4357 4-kinase inhibitor @entity2307 (10 microm) slowed or blocked the recovery of agonist-induced gM suppression. This effect could not be attributed to an action of @entity2307 on @entity19077 or on @entity4357 3-kinase. Inhibition of PIP2 synthesis at an earlier point in the lipid cycle by the use of @entity51950 (40 microm) to inhibit @entity2366 kinase also slowed the rate of recovery of successive @entity855 responses. This effect required several applications of agonist to deplete levels of various phospholipid intermediates in the lipid cycle. PIP2 antibodies attenuated the suppression of gM by agonists. Intracellular application of 20 microm PIP2 slowed the rundown of @entity29169 currents expressed in COS-1 or tsA-201 cells, and 100 microm PIP2 produced a small potentiation of native M-current bullfrog sympathetic neurons. These are the results that might be expected if agonist-induced activation of PLC and the concomitant depletion of PIP2 contribute to the excitatory action of neurotransmitters that suppress gM.

Experiments to test the role of XXXX in neurotransmitter-induced M-channel closure in bullfrog sympathetic neurons.

@entity2366 :: ('CHEBI:41847', 'Chemical') :: ['diacylglycerol'] @entity51950 :: ('MESH:C047505', 'Chemical') :: ['R59022'] @entity19077 :: ('4638', 'Gene') :: ['myosin light chain kinase'] @entity1078 :: ('CHEBI:18348', 'Chemical') :: ['phosphatidylinositol 4,5-bisphosphate'] @entity2307 :: ('MESH:C009687', 'Chemical') :: ['wortmannin'] @entity29169 :: ('3785;3786', 'Gene') :: ['KCNQ2/3'] @entity4357 :: ('MESH:D010716', 'Chemical') :: ['phosphatidylinositol'] @entity855 :: ('MESH:D000255', 'Chemical') :: ['ATP'] @entity19260 :: ('CHEBI:24846', 'Chemical') :: ['inositol phosphate']
@entity1078 :: (CHEBI:18348,Chemical) :: ['phosphatidylinositol 4,5-bisphosphate']
