ION SELECTIVITY OF PORCINE SKELETAL-MUSCLE CA2+ RELEASE CHANNELS IS UNAFFECTED BY THE ARG(615) TO CYS(615) MUTATION

The Arg(615) to Cys(615) mutation of the sarcoplasmic reticulum (SR) C a2+ release channel of malignant hyperthermia susceptible (MHS) pigs r esults in a decreased sensitivity of the channel to inhibitory Ca2+ co ncentrations. To investigate whether this mutation also affects the io n selectivity filter of the channel, the monovalent cation conductance s and ion permeability ratios of single Ca2+ release channels incorpor ated into planar lipid bilayers were compared. Monovalent cation condu ctances 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 conductan ces of MHS and normal Ca2+ release channel were not significantly diff erent for any of the monovalent cations tested. Permeability ratios me asured under biionic conditions had the permeability sequence Ca2+ >> Li+ > Na+ > K+ greater than or equal to Rb+ > Cs+, with no significant difference noted between MHS and normal channels. This systematic exa mination of the conduction properties of the pig skeletal muscle Ca2release channel indicated a higher Ca2+ selectivity (P-Ca(2+):P-K(+) a pproximately 15.5) than the sixfold Ca2+ selectivity previously report ed for rabbit skeletal (Smith et at., 1988) or sheep cardiac muscle (T inker et al.,1992) Ca2+ release channels. These results also indicate that although Ca2+ regulation of Ca2+ release channel activity is alte red, the Arg(615) to Cys(615) mutation of the porcine Ca2+ release cha nnel does not affect the conductance or ion selectivity properties of the channel.