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Nicotinamide‐adenine dinucleotide regulates muscarinic receptor‐coupled K+ (M) channels in rodent NG108‐15 cells.
Author(s) -
Higashida H,
Robbins J,
Egorova A,
Noda M,
Taketo M,
Ishizaka N,
Takasawa S,
Okamoto H,
Brown D A
Publication year - 1995
Publication title -
the journal of physiology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.802
H-Index - 240
eISSN - 1469-7793
pISSN - 0022-3751
DOI - 10.1113/jphysiol.1995.sp020520
Subject(s) - nad+ kinase , nicotinamide adenine dinucleotide , cyclic adp ribose , nicotinamide , acetylcholine , chemistry , muscarinic acetylcholine receptor , intracellular , endocrinology , biophysics , receptor , medicine , biochemistry , biology , enzyme , microbiology and biotechnology , cd38 , stem cell , cd34
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.