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

H. Higashida, J. Robbins, A. Egorova, Mami 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

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NAD
Cholinergic Agents
Cyclic ADP-Ribose
Rodentia
Streptozocin
Niacinamide
Muscarinic Receptors
Neuroblastoma
Glioma
Acetylcholine

All Science Journal Classification (ASJC) codes

  • Physiology

Cite this

Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells. / Higashida, H.; Robbins, J.; Egorova, A.; Noda, Mami; Taketo, M.; Ishizaka, N.; Takasawa, S.; Okamoto, H.; Brown, D. A.

In: The Journal of Physiology, Vol. 482, No. 2, 15.01.1995, p. 317-323.

Research output: Contribution to journalArticle

Higashida, H, Robbins, J, Egorova, A, Noda, M, Taketo, M, Ishizaka, N, Takasawa, S, Okamoto, H & Brown, DA 1995, 'Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells.', The Journal of Physiology, vol. 482, no. 2, pp. 317-323. https://doi.org/10.1113/jphysiol.1995.sp020520
Higashida, H. ; Robbins, J. ; Egorova, A. ; Noda, Mami ; Taketo, M. ; Ishizaka, N. ; Takasawa, S. ; Okamoto, H. ; Brown, D. A. / Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells. In: The Journal of Physiology. 1995 ; Vol. 482, No. 2. pp. 317-323.
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