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

Abstract

Purpose of reviewA 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 Tchannel inhibition in particular in the mechanisms of action of anesthetics and analgesics. Recent findingsRecent 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.

Readiness of nociceptor cell bodies to generate spontaneous activity results from background activity of diverse ion channels and high input resistance

“…In addition, we tested inhibitors of VGCCs that underlie T-type, L-type, and N-type Ca 2+ currents having known roles in nociceptor function and pain. 31,36 Neither an inhibitor of T-type current, TTA-P2, 15 nor of L-type current, nimodipine, 58 had significant effects on the amplitude or frequency of either smaller or larger DSFs (Tables 1 and 2). However, a relatively specific inhibitor of N-type current, ω-conotoxin GVIA, 38,47 decreased the amplitude and frequency of larger DSFs by 6.2% and 26.8%, respectively (Table 2).…”

Readiness of nociceptor cell bodies to generate spontaneous activity results from background activity of diverse ion channels and high input resistance

“…In addition, we tested inhibitors of VGCCs that underlie T-type, L-type, and N-type Ca 2+ currents having known roles in nociceptor function and pain 30,35 . Neither an inhibitor of T-type current, TTA-P2 14 , nor of L-type current, nimodipine 57 , had significant effects on the amplitude or frequency of either smaller or larger DSFs (Tables 1 and 2).…”