Ketamine and calcium signaling—a crosstalk for neuronal physiology and pathology

Abstract

Ketamine is a non‐competitive antagonist of NMDA (N‐methyl‐D‐aspartate) receptor, which has been in clinical practice for over a half century. Despite recent data suggesting its harmful side effects, such as neuronal loss, synapse dysfunction or disturbed neural network formation, the drug is still applied in veterinary medicine and specialist anesthesia. Several lines of evidence indicate that structural and functional abnormalities in the nervous system caused by ketamine are crosslinked with the imbalanced activity of multiple Ca2+‐regulated signaling pathways. Due to its ubiquitous nature, Ca2+ is also frequently located in the center of ketamine action, although the precise mechanisms underlying drug’s negative or therapeutic properties remain mysterious for the large part. This review seeks to delineate the relationship between ketamine‐triggered imbalance in Ca2+ homeostasis and functional consequences for downstream processes regulating key aspects of neuronal function.