Effect of Halothane on Human Skeletal Muscle Sarcoplasmic Reticulum Calcium-Release Channel
In order to gain an understanding of how anesthetics alter muscle function, we have utilized the planar lipid bilayer technique for recording the conductance and gating properties of a calcium-release channel molecule derived from native skeletal muscle sarcoplasmic reticulum membranes. The incorporation of this protein molecule into an artificial membrane simplifies investigation, limiting anesthetic action to the bilayer itself and/or the single protein molecule. Thus, any effect the anesthetic has on the protein’s conductance and gating functions will be a consequence of the anesthetic’s action directly on the protein and/or on the lipid bilayer in such a way as to alter the protein’s function. Our attempts to understand a piece of the puzzle of anesthetic action on skeletal muscle do, in fact, begin at the molecular, single protein level of attack and even so, this experimental model is far from simple, and the possible ways by which volatile anesthetics could alter its function represent a challenge. Our piece of the puzzle involves a large protein molecule located in the structure bridging the transverse tubule and the terminal cisternae of the sarcoplasmic reticulum (see Chapter 1, figure 1). This protein, sometimes referred to as the ryanodine receptor protein, is thought to play a significant role in excitation-contraction coupling of skeletal muscle. In our present studies, we have incorporated this protein into a planar lipid bilayer and have recorded and measured its properties as a cation-conducting channel. These studies parallel those on the pharmacogenetic disease malignant hyperthermia (MH) and illustrate how such a disease may lead to a better understanding of normal muscle response to volatile anesthetics.
KeywordsSarcoplasmic Reticulum Release Channel Volatile Anesthetic Malignant Hyperthermia Malignant Hyperthermia
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