Ion selectivity of porcine skeletal muscle Ca2+ release channels is unaffected by the Arg615 to Cys615 mutation.
The Arg615 to Cys615 mutation of the sarcoplasmic reticulum (SR) Ca2+ release channel of malignant hyperthermia susceptible (MHS) pigs results in a decreased sensitivity of the channel to inhibitory Ca2+ concentrations. To investigate whether this mutation also affects the ion selectivity filter of the channel, the monovalent cation conductances and ion permeability ratios of single Ca2+ release channels incorporated into planar lipid bilayers were compared. Monovalent cation conductances in symmetrical solutions were: Li+, 183 pS +/- 3 (n = 21); Na+, 474 pS +/- 6 (n = 29); K+, 771 pS +/- 7 (n = 29); Rb+, 502 pS +/- 10 (n = 22); and Cs+, 527 pS +/- 5 (n = 16). The single-channel conductances of MHS and normal Ca2+ release channel were not significantly different for any of the monovalent cations tested. Permeability ratios measured under biionic conditions had the permeability sequence Ca2+ >> Li+ > Na+ > K+ > or Rb+ > Cs+, with no significant difference noted between MHS and normal channels. This systematic examination of the conduction properties of the pig skeletal muscle Ca2+ release channel indicated a higher Ca2+ selectivity (PCa2+:Pk+ approximately 15.5) than the sixfold Ca2+ selectivity previously reported for rabbit skeletal (Smith et al., 1988) or sheep cardiac muscle (Tinker et al., 1992) Ca2+ release channels. These results also indicate that although Ca2+ regulation of Ca2+ release channel activity is altered, the Arg615 to Cys615 mutation of the porcine Ca2+ release channel does not affect the conductance or ion selectivity properties of the channel.
Shomer
N H
NH
Department of Veterinary PathoBiology, University of Minnesota, St. Paul 55108.
Mickelson
J R
JR
Louis
C F
CF
D000818:Animals; D001120:Arginine; D002118:Calcium / Q000378:metabolism; D015220:Calcium Channels / Q000096:biosynthesis / Q000235:genetics / Q000502:physiology*; D002414:Cations, Monovalent / Q000378:metabolism; D003545:Cysteine; D004553:Electric Conductivity; D007700:Kinetics; D008051:Lipid Bilayers; D008305:Malignant Hyperthermia / Q000235:genetics / Q000662:veterinary; D009132:Muscles / Q000502:physiology*; D017354:Point Mutation; D012519:Sarcoplasmic Reticulum / Q000502:physiology*; D013552:Swine; D013553:Swine Diseases; D013997:Time Factors
D015220:Calcium Channels; D002414:Cations, Monovalent; D008051:Lipid Bilayers; D001120:Arginine; D003545:Cysteine; D002118:Calcium