Subcellular distribution of an inhalational anesthetic in situ

Journal Article · Mon Jan 01 04:00:00 EST 1990 · Proceedings of the National Academy of Sciences of the United States of America; (USA)

DOI:https://doi.org/10.1073/pnas.87.1.454· OSTI ID:6983701

Eckenhoff, R G; Shuman, H ^[1]

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1. Univ. of Pennsylvania Medical Center, Philadelphia (USA)

To better understand the mechanisms and sites of anesthetic action, we determined the subcellular partitioning of halothane in a tissue model. A method was found to fix the in vivo distribution of halothane in rat atrial tissue for subsequent electron microscopy and x-ray microanalysis. Atrial strips were exposed to various concentrations of halothane, rapidly frozen, cryo-sectioned, and cryo-transferred into an electron microscope. Irradiation of the hydrated cryosections with the electron beam caused halothane radiolysis, which allowed retention of the halogen-containing fragments after dehydration of the sections. The bromine from halothane was detected and quantified with x-ray microanalysis in various microregions of atrial myocytes. Halothane (bromine) partitioned largely to mitochondria, with progressively lower concentrations in sarcolemma, nuclear membrane, cytoplasm, sarcomere, and nucleus. Partitioning could not be explained solely by distribution of cellular lipid, suggesting significant and differential physicochemical solubility in protein. However, we found no saturable compartment in atrial myocytes within the clinical concentration range, which implies little specific protein binding.

• OSTI ID: 6983701
• Journal Information: Proceedings of the National Academy of Sciences of the United States of America; (USA), Journal Name: Proceedings of the National Academy of Sciences of the United States of America; (USA) Vol. 87:1; ISSN 0027-8424; ISSN PNASA
• Country of Publication: United States
• Language: English

Related Subjects

550602* -- Medicine-- External Radiation in Diagnostics-- (1980-)
62 RADIOLOGY AND NUCLEAR MEDICINE
ANESTHETICS
ANIMALS
BIOLOGICAL MODELS
BODY
CARDIOVASCULAR SYSTEM
CELL CONSTITUENTS
CENTRAL NERVOUS SYSTEM DEPRESSANTS
CHEMICAL ANALYSIS
DISTRIBUTION
DRUGS
ELECTRON MICROPROBE ANALYSIS
ELECTRON MICROSCOPY
HEART
IN VITRO
IN VIVO
MAMMALS
MICROANALYSIS
MICROSCOPY
MUSCLES
MYOCARDIUM
ORGANOIDS
ORGANS
RATS
RODENTS
SUBCELLULAR DISTRIBUTION
VERTEBRATES