Effects of the halothane-sensitivity gene on sarcoplasmic reticulum function
J. R. Mickelson, E. M. Gallant, W. E. Rempel, K. M. Johnson, L. A. Litterer, B. A. Jacobson and C. F. Louis Department of Veterinary Biology, University of Minnesota, St. Paul 55108. Pigs heterozygous for the halothane-sensitivity gene exhibit a distinct phenotype with regard to both in vivo and in...
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Veröffentlicht in: | American Journal of Physiology: Cell Physiology 1989-10, Vol.257 (4), p.C787-C794 |
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Zusammenfassung: | J. R. Mickelson, E. M. Gallant, W. E. Rempel, K. M. Johnson, L. A. Litterer, B. A. Jacobson and C. F. Louis
Department of Veterinary Biology, University of Minnesota, St. Paul 55108.
Pigs heterozygous for the halothane-sensitivity gene exhibit a distinct
phenotype with regard to both in vivo and in vitro muscle responses to
halothane (E. M. Gallant, J. R. Mickelson, B. D. Roggow, S. K. Donaldson,
C. F. Louis, and W. E. Rempel. Am. J. Physiol. 257 (Cell Physiol. 26):
C781-C786, 1989). In this paper heavy sarcoplasmic reticulum (SR)
preparations were isolated from the muscles of pigs of all three genotypes.
The rate of calcium release from SR of pigs homozygous for the
halothane-sensitivity gene was approximately twice that of SR from pigs
homozygous for the normal allele. Furthermore, in the presence of 6 microM
Ca2+, the binding of [3H]ryanodine to SR isolated from the homozygous
halothane-sensitive pigs was of a higher affinity than was the binding to
SR isolated from the homozygous normal pigs (Kd = 70-90 vs. 265 nM,
respectively). The SR from pigs heterozygous for the halothane-sensitivity
gene, however, demonstrated intermediate values for the rate of calcium
release and the affinity for [3H]ryanodine (Kd = 192 nM). Thus the
alterations in heavy SR calcium release and [3H]ryanodine binding in the
pigs containing one copy of the halothane-sensitivity gene demonstrate a
distinct heterozygote phenotype. These data also suggest that the protein
product of this gene is closely associated with, and perhaps identical to,
the SR calcium release channel-ryanodine receptor protein. |
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ISSN: | 0363-6143 0002-9513 1522-1563 |
DOI: | 10.1152/ajpcell.1989.257.4.C787 |