A Comparative Study of Cell Specific Effects of Systemic and Volatile Anesthetics on Identified Motor Neurons and Interneurons of Lymnaea stagnalis (L.), Both in the Isolated Brain and in Single Cell Culture

Abstract

1. A comparative descriptive analysis of systemic (sodium pentobarbital, sodium thiopentone, ketamine) and volatile (halothane, isoflurane, enflurane) general anesthetics revealed important differences in the neuronal responses of identified motor neurons and interneurons in the isolated central nervous system (CNS) and cultured identified neurons in single cell culture of Lymnaea stagnalis (L.). 2. At high enough concentrations all anesthetics eventually caused cessation of spontaneous or evoked action potentials, but volatile anesthetics were much faster acting. Halothane at low concentrations caused excitation, thought to be equivalent to the early excitatory phase of anesthesia. Strong synaptic inputs were not always abolished by pentobarbital. 3. There were cell specific concentration-dependent responses to halothane and pentobarbital in terms of membrane potential, action potential characteristics, the after hyperpolarization and patterned activity. Individual neurons generated specific responses to the applied anesthetics. 4. The inhalation anesthetics, enflurane, and isoflurane, showed little concentration dependence of effect, in contrast to results obtained with halothane. Enflurane was faster acting than halothane and isoflurane was particularly different, producing quiescence in all cells types studied at all concentrations studied. 5. Halothane, enflurane, the barbiturate general anesthetics, pentobarbital, and sodium thiopentone and the dissociative anesthetic ketamine, produced two distinctly different effects which could be correlated with cell type and their location in the isolated brain: either a decline in spontaneous and evoked activity prior to quiescence in interneurons or paroxysmal depolarizing shifts (PDS) in motor neurons, again prior to quiescence, which were reversed when the anesthetic was eliminated from the bath. In the strongly electrically coupled motor neurons, VD1 and RPD2, both types of response were observed, depending on the anesthetic used. Thus, with the exception isoflurane, all the motor neurons subjected to the anesthetic agents studied here were capable of generating PDS in situ , but the interneurons did not do so. 6. The effects of halothane on isolated cultured neurons indicates that PDS can be generated by single identified neurons in the absence of synaptic inputs. Further, many instances of PDS in neurons that do not generate it in situ have been found in cultured neurons. The nature of PDS is discussed.

Volatile Anesthetics and O2 Activate TASK-1/3 by Weak H-Bonding with X-Gate Uncharged Arg-245: The Major Molecular Mechanism for Carotid Body Hypoxic Sensitivity and Further Insights into Fighter Pilot +Gz-Induced LOC

“…5,46,47 Arguments against unitary models arise from VA interference with a multitude of sites and systems. There has been considerable interest in effects on voltage-gated-calcium-channels (VGCC), 48,49,50,51 γ-aminobutyric acid receptors (GABA A R), 52 sodium channels (Na v ) 3,53,54 and potassium channels, 40,55,56 to name a few. There is also interest in the mechanisms of VA effects on the cardiovascular system.…”

The Use of Isoflurane and Adjunctive Magnesium Chloride Provides Fast, Effective Anaesthetization of Octopus vulgaris

“…There is a fuller discussion of the mode of action of magnesium salts as muscle relaxants elsewhere [5], but it should be noted that MgCl 2 may also be a mild central sedative analgesic [17,18]. However, in our view, volatile anaesthetics are preferable, and isoflurane has proved successful for anaesthetising Octopus vulgaris [5,19]. Isoflurane is a non-flammable halogenated ether compound used by both clinicians and veterinarians.…”

“…Properties of general anaesthetics. Clinical anaesthetics, such as isoflurane and related compounds, have well-known systemic and cellular actions, which have been demonstrated on mammals and on gastropod molluscs such as Lymnaea stagnalis [19] and on Octopus vulgaris [20]. They include ion channels and voltage-gated channels for sodium, potassium, and calcium and tend to block synaptic transmission [21].…”