Magnesium Sulfate Enhances Non-depolarizing Muscle Relaxant Vecuronium Action at Adult Muscle-type nicotinic Acetylcholine Receptor in Vitro

I have read social media articles about the importance of acetylcholine (ACh) for muscles and memory. Since cholinergic drugs can inhibit, enhance, or mimic the action of the neurotransmitter acetylcholine, I wanted to find a study that showed the different effects of acetylcholine on receptors. I found a study that examines the long-term effects of magnesium sulfate (MgSO4) in the treatment of eclampsia or placenta previa, which allows anesthesiologists to treat obstetric patients with hypermagnesemia disorder. This is an experimental research because more than one group is created, followed by a manipulation of a given experience for these groups, and a measurement of the influence of the manipulation. I think the study was well designed since it used different doses of each drug and used figures that were helpful to explain the results. Some studies have suggested that MgSO4 has a presynaptic effect by inhibiting acetylcholine release at motor nerve terminals. This study hypothesizes that MgSO4 interacts with Vecuronium, a non-depolarizing muscle relaxant used for general anesthesia. The goal of the study is to investigate the effect of MgSO4 and its interaction with vecuronium at adult muscle-type acetylcholine receptors in vitro.   

For methodology, six plasmids were first expressed with encoded complementary DNA sequences for the muscle nicotinic ACh receptor subunits. Human embryonic kidney 293 (HEK293) cells were cultured in Dulbecco’s modified Eagle’s medium and were supplemented with calf serum, penicillin, and streptomycin at 37 Celsius in a 5% CO2 incubator. Then, cells were transfected with Lipofectamine 2000 according to the manufacturer’s protocol. Afterward, the transfected cells were incubated for 24 hr before the recordings were made. HEK293 cells were voltage-clamped using the whole-cell patch-clamp technique. The test solutions were applied to HEK293 cells and the peak current was determined. The washout time for each drug application was at least sixty seconds. Data analysis was performed offline using Origin 8 and Graph Pad Prism 4.  

The first result showed that MgSO4 inhibited adult muscle-type acetylcholine receptors. Then, the inhibitory effect of magnesium sulfate was studied in more detail to reveal that the peak inward currents were dependent on the acetylcholine concentrations. The inward currents evoked from the nicotinic acetylcholine receptors were reduced when magnesium sulfate was applied at the doses of 3 mmol/L and 30 mmol/L. However, the inhibition produced by magnesium sulfate was not affected by increasing the concentration of acetylcholine. The second result showed that vecuronium inhibited adult muscle-type acetylcholine receptors. 10 nmol/L of vecuronium produced an inhibition when an acetylcholine agonist at a concentration of 1 micromol/L was used. However, when researchers used 100 micromol/L of acetylcholine agonist, the inhibition was decreased confirming competitive inhibition. The third result showed that the interaction between magnesium sulfate at different concentrations and vecuronium led to a strong enhancement of the 10 nmol/L vecuronium induced inhibition. In conclusion, this study found that “the presence of magnesium in the range of therapeutic serum concentrations could significantly intensify the potency of vecuronium on adult muscle-type acetylcholine receptors” (Wang, 1458). Furthermore, this suggests that the interaction between magnesium and non-depolarizing muscle relaxants on adult muscle-type acetylcholine receptors could be one of the reasons why magnesium enhances a non-depolarizing muscle relaxants-induced neuromuscular blockade.   

References

Wang, H., et al. “Magnesium Sulfate Enhances Non-depolarizing Muscle Relaxant Vecuronium Action at Adult Muscle-type nicotinic Acetylcholine Receptor in Vitro.” Nature News, Nature Publishing Group, 10 October 2011.