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Streptozotocin, an inducer of NAD+ decrease, attenuates M-potassium current inhibition by ATP, bradykinin,
H Higashida1, A Egorova, N Hoshi
1Department of Biophysics, Kanazawa University School of Medicine, Japan.
Abstract:
The M-potassium current was inhibited by bath application of 100 micron ATP, 10 nM bradykinin, 100 nM angiotensin II and 100 nM endothelin 1 as well as by 10 micron acetylcholine in an m1-muscarinic acetylcholine receptor-transformed NG108-15 cell line. The inhibition of M-current was attenuated in cells pretreated with 5 mM streptozotocin for 5-15 h and restored by simultaneous incubation with 5 mM nicotinamide. The results suggest that signal transduction from these five different receptors to M channels shares a common pathway which is susceptible to a streptozotocin-induced decrease in cellular NAD+ content.
Insights
Five different receptors inhibit M-potassium current via a common pathway. This pathway
Area of Science:
- Neuroscience
- Cellular Signaling
Background:
- The M-potassium current plays a crucial role in neuronal excitability.
- Understanding the regulation of M-current is vital for comprehending neuronal function.
Purpose of the Study:
- To investigate the signal transduction pathways involved in M-potassium current inhibition.
- To identify commonalities in the signaling cascades initiated by various receptor types.
Main Methods:
- Utilized an m1-muscarinic acetylcholine receptor-transformed NG108-15 cell line.
- Applied ATP, bradykinin, angiotensin II, endothelin 1, and acetylcholine to inhibit M-current.
- Investigated the effects of streptozotocin and nicotinamide pretreatment on M-current inhibition.
Main Results:
- ATP, bradykinin, angiotensin II, endothelin 1, and acetylcholine all inhibited the M-potassium current.
- Pretreatment with streptozotocin attenuated this inhibition.
- Simultaneous incubation with nicotinamide restored the M-current inhibition.
Conclusions:
- A shared signaling pathway mediates the inhibition of M-current by these five distinct receptors.
- This common pathway is sensitive to a decrease in cellular NAD+ content induced by streptozotocin.