Reconstitution of abnormalities in the malignant hyperthermia-susceptible pig ryanodine receptor

• DOI: 10.1152/ajpcell.1993.264.1.c125
• Publication Date: 2017-12-24T13:52:36Z
• Authors: N. H. Shomer; C. F. Louis; M. Fill; L. A. Litterer; J. R. Mickelson
• Keywords: Malignant hyperthermia

Malignant hyperthermia-susceptible (MHS) pigs homozygous for the Cys615 ryanodine receptor allele demonstrate altered sarcoplasmic reticulum (SR) binding and Ca2+ release channel regulatory properties when compared with normal Arg615 allele. While solubilized in 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate, purified MHS receptors had a similar dissociation constant (Kd) ryanodine, maximum binding, concentration half-maximal stimulation inhibition of (Ca2+(0.5)); however, after reconstitution into proteoliposomes, Kd values 75 150 nM, respectively, which were significantly different. The porcine also single-channel Cs+ conductance, optimal cis-Ca2+ opening, cis-Ca2+(0.5) activation. Significantly, at inactivating levels (> 0.1 mM), channels greater open probability, higher opening (250 vs. microM normal, respectively), longer mean times, shorter closed times than did channels. We conclude that mutation residue 615 causes detectable alteration receptor/Ca2+ activity thus may represent primary defect responsible SR regulation characteristic muscle.