Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells.

H. Higashida, J. Robbins, A. Egorova, M. Noda, M. Taketo, N. Ishizaka, S. Takasawa, H. Okamoto, D. A. Brown

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Abstract

1. The possible role of nicotinamide‐adenine dinucleotide (NAD+) and cyclic adenosine diphosphate ribose (cADPR) as regulators of M‐type K+ currents (IK(M)) has been studied in whole‐cell patch‐clamped NG108‐15 mouse neuroblastoma x rat glioma cells that had been transformed to express m1 muscarinic acetylcholine receptors (mAChRs). 2. Pre‐incubation of NG108‐15 cells for 6‐8 h with streptozotocin (2‐5 mM) reduced NAD+ levels by 40‐50%. Nicotinamide (2‐5 mM) increased NAD+ levels and prevented depletion by streptozotocin. 3. Streptozotocin pretreatment reduced the inhibition of IK(M) produced by 100 microM acetylcholine (ACh) from 51.6 +/‐ 7.0 to 29.1 +/‐ 7.5%. This was prevented by simultaneous pre‐incubation with 2 mM nicotinamide or by adding 2 mM NAD+ to the pipette solution. Neither procedure significantly affected the initial amplitude of IK(M). 4. Inclusion of 2 microM cADPR in the pipette solution induced a slow loss of IK(M) with a time constant of about 20 min. 5. It is concluded that mAChR‐induced inhibition of IK(M) requires intracellular NAD+. This might be needed for the formation of cADPR as a regulator or messenger for IK(M) inhibition.

Original languageEnglish
Pages (from-to)317-323
Number of pages7
JournalThe Journal of Physiology
Volume482
Issue number2
DOIs
Publication statusPublished - Jan 15 1995
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Physiology

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    Higashida, H., Robbins, J., Egorova, A., Noda, M., Taketo, M., Ishizaka, N., Takasawa, S., Okamoto, H., & Brown, D. A. (1995). Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells. The Journal of Physiology, 482(2), 317-323. https://doi.org/10.1113/jphysiol.1995.sp020520