Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells

H Higashida; D A Brown; J Robbins

doi:10.1007/s004240000433

Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells

H Higashida, D A Brown, J Robbins

Wolfson SPaRC

Research output: Contribution to journal › Article › peer-review

19 Citations (Scopus)

Abstract

The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to I-K(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 (less than or equal to 10 muM), the latter by WAY123,398 (less than or equal to 10 muM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 muM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 muM) 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 muM), 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 M-1 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 M-1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.

Original language	English
Pages (from-to)	228 - 234
Number of pages	7
Journal	Pfl�s Archiv / European Journal of Physiology
Volume	441
Issue number	2-3
DOIs	https://doi.org/10.1007/s004240000433
Publication status	Published - 2000

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@article{2e568be23b704959991ff7ddb868460b,

title = "Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells",

abstract = "The {"}M-like{"} current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to I-K(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 (less than or equal to 10 muM), the latter by WAY123,398 (less than or equal to 10 muM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 muM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 muM) 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 muM), 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 M-1 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 M-1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.",

author = "H Higashida and Brown, {D A} and J Robbins",

year = "2000",

doi = "10.1007/s004240000433",

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journal = "Pfl�s Archiv / European Journal of Physiology",

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T1 - Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells

AU - Higashida, H

AU - Brown, D A

AU - Robbins, J

PY - 2000

Y1 - 2000

N2 - The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to I-K(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 (less than or equal to 10 muM), the latter by WAY123,398 (less than or equal to 10 muM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 muM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 muM) 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 muM), 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 M-1 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 M-1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.

AB - The "M-like" current in NG108-15 cells has two components carried by different K+ channels: a fast-deactivating component, analogous to I-K(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 (less than or equal to 10 muM), the latter by WAY123,398 (less than or equal to 10 muM). Bradykinin (100 nM) inhibited 76% of the KCNQ component of current compared with 12% of the merg component. Cyclic ADP ribose (cADPR, 2 muM), introduced via the patch pipette, caused a rundown of both current components. Acetylcholine (100 muM) 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 muM), 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 M-1 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 M-1-muscarinic inhibition of both KCNQ2/3 and merg1 channels.

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JO - Pfl�s Archiv / European Journal of Physiology

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Both linopirdine- and WAY123,398-sensitive components of I-K(M,I-ng) are modulated by cyclic ADP ribose in NG108-15 cells

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