Abstract
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.
This is a preview of subscription content, log in via an institution.
Buying options
Tax calculation will be finalised at checkout
Purchases are for personal use only
Learn about institutional subscriptionsPreview
Unable to display preview. Download preview PDF.
References
M. G. Larach, Standardization of the caffeine halothane muscle contracture test, Anesth Analg 69:511–515 (1989).
M. Fill, E. Stefani and T. E. Nelson, Abnormal human sarcoplasmic reticulum Ca2+ release channels in malignant hyperthermia skeletal muscle, Biophys J (in press).
L. L. Firestone, J. C. Miller and K. W. Miller, Appendix: Tables of physcial and pharmacological properties of anesthetics, in: “Molecular and Cellular Mechanisms of Anesthetics,” S. H. Roth and K. W. Miller, eds., Plenum Publishing, New York (1986) p. 455.
J. S. Smith, T. Imagawa, J. J. Ma, M. Fill, K. Campbell and R. Coronado, Purified ryanodine receptor from rabbit skeletal muscle is the calcium release channel of the sarcoplasmic reticulum, J Gen Physiol 92:1–26 (1988).
M. Fill, J. R. Coronado, J. Mickelson, J. M. Vilven, B. A. Jacobson and C. F. Louis, Abnormal ryanodine receptor channels in malignant hyperthermia, Biophys J 57:471–476 (1990).
A. Saito, M. Inui, M. Radenmacher, J. Frank and S. Fleischer, Ultrastructure of the calcium release channel of sarcoplasmic reticulum, J Cell Biol 107:211–219 (1988).
T. E. Nelson and T. Sweo, Ca2+ uptake and Ca2+ release by skeletal muscle sarcoplasmic reticulum: Differing sensitivity to inhalational anesthetics. Anesthesiology 69:571–577 (1988).
T. E. Nelson, Effect of calmodulin on calcium pulse-induced calcium release from fragmented skeletal sarcoplasmic reticulum, Fed Proc 43:498 (1984).
G. Meissner, Evidence for a role for calmodulin in the regulation of calcium release from skeletal muscle sarcoplasmic reticulum, Biochemistry 25:244–250 (1986).
S. T. Ohnishi, Calcium-induced calcium release from fragmented sarcoplasmic reticulum, J Biochem 86:1147–1150 (1979).
G. Meissner, Adenine nucleotide stimulation of Ca2+-induced Ca2+ release in sarcoplasmic reticulum, J Biol Chem 259:2365–2374 (1984).
H. Takeshima, S. Nishimura, T. Matsumoto, H. Ishida, K. Kangawa, N. Minamino, N. Mastuo, M. Ueda, M. Hanaoka, T. Hirose and S. Numa, Primary structure and expression from complementary DNA of skeletal muscle ryanodine receptor, Nature 339:439–445 (1989).
T. E. Nelson and M. A. Denborough, Studies on normal human skeletal muscle in relation to the pathopharmacology of malignant hyperpyrexia, Clin Exp Pharm Physiol 4:315–322 (1977.)
F. R. Ellis, D. G. F. Harriman, N. P. Keany, Kyei-Mensah and J. H. Tyrrell, Halothane-induced muscle contracture as a cause of hyperpyrexia. Brit J Anaesth 43:721–722 (1971).
Author information
Authors and Affiliations
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 1991 Plenum Press, New York
About this chapter
Cite this chapter
Nelson, T.E. (1991). Effect of Halothane on Human Skeletal Muscle Sarcoplasmic Reticulum Calcium-Release Channel. In: Blanck, T.J.J., Wheeler, D.M. (eds) Mechanisms of Anesthetic Action in Skeletal, Cardiac, and Smooth Muscle. Advances in Experimental Medicine and Biology, vol 301. Springer, Boston, MA. https://doi.org/10.1007/978-1-4684-5979-1_3
Download citation
DOI: https://doi.org/10.1007/978-1-4684-5979-1_3
Publisher Name: Springer, Boston, MA
Print ISBN: 978-1-4684-5981-4
Online ISBN: 978-1-4684-5979-1
eBook Packages: Springer Book Archive