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Query: UMLS:C0848283 (rundown)
 502 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to IK(M) in sympathetic neurones and carried by KCNQ2/3 channels, and a more slowly deactivating component carried by murine erg1 (merg1) channels. The former is selectively blocked by linopirdine (< or =10 microM), the latter by WAY123,398 (< or =10 microM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 microM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 microM) inhibited 89% of the KCNQ component of current compared to 34% of the merg component. After 15 min of intracellular dialysis with the cADPR antagonist 8-amino-cADP ribose (100 microM), the inhibition reduced to 40% and 19% and after 30 min it was further reduced to 8% and 5% for the KCNQ currents and merg currents respectively. These data show that both KCNQ and merg currents in NG108-15 cells can be modulated by either bradykinin or M1 muscarinic receptors. The inhibition of the KCNQ current component is more pronounced than that of the merg component. These results suggest that cADPR might be involved in M1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.
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PMID:Both linopirdine- and WAY123,398-sensitive components of I K(M,ng) are modulated by cyclic ADP ribose in NG108-15 cells. 1121 Nov 7

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 ATP involves phospholipase C (PLC). The present results are consistent with the involvement of the lipid and inositol phosphate cycles in the effects of both P2Y and muscarinic cholinergic agonists on gM. Impairment of resynthesis of phosphatidylinositol 4,5-bisphosphate (PIP2) with the phosphatidylinositol 4-kinase inhibitor wortmannin (10 microm) slowed or blocked the recovery of agonist-induced gM suppression. This effect could not be attributed to an action of wortmannin on myosin light chain kinase or on phosphatidylinositol 3-kinase. Inhibition of PIP2 synthesis at an earlier point in the lipid cycle by the use of R59022 (40 microm) to inhibit diacylglycerol kinase also slowed the rate of recovery of successive ATP 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 KCNQ2/3 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.
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PMID:Experiments to test the role of phosphatidylinositol 4,5-bisphosphate in neurotransmitter-induced M-channel closure in bullfrog sympathetic neurons. 1283 15