Are Local Anesthetics and General Anesthetics Different?

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It is widely believed that general and local anesthetics act by different mechanisms. While there is general agreement that the mode of action of general anesthetics is poorly understood, local anesthetics are believed to block voltage-gated sodium channels and thereby affect action potentials in nerves. Here, we demonstrate that general and local anesthetics display an identical influence on the physical properties of membranes, suggesting a physical mechanism for both classes of anesthetics. In calorimetric experiments we found that both general and local anesthetics lower the melting point of lipids via a mechanism known as freezing-point depression. We have recently proposed a theory for anesthesia that is based on the influence of anesthetics on melting transitions (Heimburg & Jackson, 2007) and the generation of electromechanical pulses (solitons) in nerve axons (Heimburg & Jackson, 2005). Since the heat capacity of membranes is closely related to membrane permeability, the presence of anesthetics has also a pronounced effect on the formation of spontaneous membrane pores known as lipid ion channels. Thus, not only general but also local anesthetics are expected to be able to block channels in lipid membranes by a completely unspecific mechanism that does not require the binding to a receptor molecule. In order to investigate the influence of general and local anesthetics on membrane permeability, we conducted electrophysiological experiments on black lipid membranes.