The Biology of General Anesthesia from Paramecium to Primate

Abstract

General anesthesia serves a critically important function in the clinical care of human patients. However, the anesthetized state has foundational implications for biology because anesthetic drugs are effective in organisms ranging from paramecia, to plants, to primates. Although unconsciousness is typically considered the cardinal feature of general anesthesia, this endpoint is only strictly applicable to a select subset of organisms that are susceptible to being anesthetized. We review the behavioral endpoints of general anesthetics across species and propose the isolation of an organism from its environment-both in terms of the afferent arm of sensation and the efferent arm of action-as a generalizable definition. We also consider the various targets and putative mechanisms of general anesthetics across biology and identify key substrates that are conserved, including cytoskeletal elements, ion channels, mitochondria, and functionally coupled electrical or neural activity. We conclude with a unifying framework related to network function and suggest that general anesthetics-from single cells to complex brains-create inefficiency and enhance modularity, leading to the dissociation of functions both within an organism and between the organism and its surroundings. Collectively, we demonstrate that general anesthesia is not restricted to the domain of modern medicine but has broad biological relevance with wide-ranging implications for a diverse array of species.

Anesthetics and plants: no pain, no brain, and therefore no consciousness

“…Anesthetics and plants Kelz and Mashour (2019) covered the many molecular targets of general anesthetics, emphasizing those targets that are conserved from single-celled organisms to humans (Fig. 1).…”

“…Additionally, the anesthetics probably target the lipid bilayers of cellularplasmamembranes(Paveletal.2020).Manyofanesthetics' "neuron-specific" effects on animals are conserved effects that have been elaborated to disrupt electrical signaling in the nervous system. In their list of conserved effects, Kelz and Mashour (2019) also included disruption of microtubules of the cell skeleton and inhibition of mitochondrial complex I, although the authors only discussed these effects in animals.…”

Consciousness as an Emergent Phenomenon: A Tale of Different Levels of Description

“…Furthermore, certain anesthetics that influence cognition and conscious experience seem to involve microtubules [ 12 ]. Relatedly, anesthetics are effective on any organism [ 99 ]. How can anesthetic inhibit some responses to the environment in unicellular organisms such as slime molds that do not even have a nervous system [ 100 , 101 ]?…”

Differential inhibition of GABA release from mouse hippocampal interneuron subtypes by the volatile anesthetic isoflurane

“…Interneuron diversity derives in part from differences in synaptic signaling protein expression (40). Several types of presynaptic proteins are affected by clinical concentrations of isoflurane, including ion channels, Ca 2+ -binding proteins, and intracellular signaling proteins (41). Other potential targets for transmitter-selective or interneuron-selective actions include K + channels, which determine neuronal excitability, AP morphology, and ultimately neurotransmitter release via membrane hyperpolarization and repolarization (42), mitochondrial electron transport complex proteins involved in presynaptic energetics (43), and presynaptic SV exocytotic proteins such as syntaxin (44).…”