Inhibition of autophagy by esketamine attenuates hypoxia/reoxygenation injury in cardiomyocytes via inhibition of Ca2+/CaMKKβ/AMPK/mTOR pathway by down-regulation of transient receptor potential vanilloid 1 expression.
Journal of physiology and pharmacology : an official journal of the Polish Physiological Society April 1, 2025 Y Zhang, Q M Lu, H C Hu et al.
Esketamine protects heart muscle cells from injury caused by a lack of oxygen followed by reoxygenation, a model of heart attack damage. The protection works by blocking a cellular cleanup process called autophagy through a specific signaling chain. Esketamine reduced cell death, lowered autophagy markers, and prevented a rise in calcium inside the cells. Increasing autophagy or calcium levels weakened esketamine's protective effect. The drug acts by inhibiting the TRPV1 calcium channel, which then suppresses the CaMKKβ/AMPK/mTOR pathway. The findings suggest esketamine could be a candidate for reducing heart damage from ischemia-reperfusion injury.