H. Higashida et al., NICOTINAMIDE ADENINE-DINUCLEOTIDE REGULATES MUSCARINIC RECEPTOR-COUPLED K-15 CELLS( (M) CHANNELS IN RODENT NG108), Journal of physiology, 482(2), 1995, pp. 317-323
1. The possible role of nicotinamide-adenine dinucleotide (NAD(+)) and
cyclic adenosine diphosphate ribose (cADPR) as regulators of M-type K
+ currents (I-K(M) has been studied in whole-cell patch-clamped NG108-
15 mouse neuroblastoma x rat glioma cells that had been transformed to
express mi muscarinic acetylcholine receptors (mAChRs). 2. Pre-incuba
tion of NG108-15 cells for 6-8 h with streptozotocin (2-5 mM) reduced
NAD(+) levels by 40-50%. Nicotinamide (2-5 mM increased NBD+ levels an
d prevented depletion by streptozotocin. 3. Streptozotocin pretreatmen
t reduced the inhibition of produced by 100 mu M acetylcholine (ACh) f
rom 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 mu M cADPR in the pipette solut
ion induced a slow loss of I-K(M) with a time constant of about 20 min
. 5. It is concluded that mAChR-induced inhibition of I-K(M) requires
intracellular NAD(+). This might be needed for the formation of cADPR
as a regulator or messenger for I-K(M) inhibition.