Are neuronal voltage-gated calcium channels valid cellular targets for general anesthetics?

Abstract

The effects of anesthetics and analgesics on ion channels have been the subject of intense research since recent reports of direct actions of anesthetic molecules on ion channel proteins. It is now known that ligand-gated channels, particularly γ-amino-butyric acid (GABAA) and N-methyl-D-aspartate (NMDA) receptors, play a key role in mediating anesthetic actions, but these channels are unable to account for all aspects of clinical anesthesia such as loss of consciousness, immobility, analgesia, amnesia, and muscle relaxation. Furthermore, an assortment of voltage-gated and background channels also display anesthetic sensitivity and a key question arises: What role do these other channels play in clinical anesthesia? These channels have overlapping physiological roles and pharmacological profiles, making it difficult to assign aspects of the anesthetic state to individual channel types. Here, we will focus on the function of neuronal voltage-gated calcium channels in mediating the effects of general anesthetics.