Local Anesthetics Modulate Neuronal Calcium Signaling through Multiple Sites of Action

Abstract

Different and overlapping sites of action of LAs are involved in inhibiting the KCl- and carbachol-evoked [Ca2+](i) transients, including voltage-dependent Ca2+ channels, a site associated with the caffeine-sensitive Ca2+ store and a possible site associated with the IP(3)-sensitive Ca2+ store, and a site in the muscarinic pathway. K+ channels, but not Na+ channels, seem to modulate the evoked [Ca2+](i) transients, as well as the LA-effects on such responses.

Local anesthetics

“…Arguments have been forwarded that local anesthetics might exert their pharmacologic action not only on sodium ion conductance, but also on other ionic conductances (e.g. potassium and calcium) [5,6].…”

Increase in intracellular Ca2+ concentration is not the only cause of lidocaine-induced cell damage in the cultured neurons of Lymnaea stagnalis

“…Although we were unable to confirm some lidocaine-induced changes, the damage to cells induced by lidocaine observed in this study could primarily be attributed to necrosis. It is generally considered that lidocaine affects the intracellular signaling pathways and cellular plasma membrane of neuronal structures [8]; therefore, it may be natural to consider that apoptosis was also progressing simultaneously.…”

“…To clarify the mechanism of local anesthetic neurotoxicity, we compared the relationship between morphological changes and elevated Ca 2+ concentrations in cells. Local anesthetics increase the intracellular Ca 2+ concentration and modulate neuronal calcium signaling through multiple sites of action [8]. In the present experiments, morphological changes in cells, such as shrinkage or the formation of rugged surfaces, were considered toxic to the cells, and were analyzed in relation to the intracellular Ca 2+ concentration.…”

Central Nervous System–Toxic Lidocaine Concentrations Unmask L-Type Ca2+ Current–Mediated Action Potentials in Rat Thalamocortical Neurons: An In Vitro Mechanism of Action Study

“…5,[21][22][23][24] To better understand whether such Na + channel-independent actions contribute to the unmasking of HT spikes in TC neurons, we investigated lidocaine's actions under conditions of robust Na + channel blockade in neurons pretreated with TTX (600 nM).…”