The role of voltage-gated calcium channels in the mechanisms of anesthesia and perioperative analgesia.

Abstract

A family of neuronal voltage-gated calcium channels (VGCCs) have received only recently a significant consideration regarding the mechanisms of anesthesia because VGCC inhibition may be important in anesthetic action by decreasing neuronal excitability and presynaptic excitatory transmission. The T-type VGCCs channels (T-channels), although rarely involved in synaptic neurotransmitter release, play an important role in controlling neuronal excitability and in generating spontaneous oscillatory bursting of groups of neurons in the thalamus thought to be involved in regulating the state of arousal and sleep. Furthermore, these channels are important regulators of neuronal excitability in pain pathway. This review will provide an overview of historic perspective and the recent literature on the role of VGCCs and T-channel inhibition in particular in the mechanisms of action of anesthetics and analgesics. Recent research in the field of novel mechanisms of hypnotic action of anesthetics revealed significant contribution of the Ca V 3.1 isoform of T-channels expressed in the thalamus. Furthermore, perioperative analgesia can be achieved by targeting Ca V 3.2 isoform of these channels that is abundantly expressed in pain pathways. The review summarizes current knowledge regarding the contribution of T-channels in hypnosis and analgesia. Further preclinical and clinical studies are needed to validate their potential for developing novel anesthetics and new perioperative pain therapies.