HETEROGENEITY OF CA2-MUSCLE AND CARDIAC RYANODINE RECEPTORS( GATING OF SKELETAL)

The single-channel activity of rabbit skeletal muscle ryanodine recept or (skeletal RyR) and dog cardiac RyR was studied as a function of cyt osolic [Ca2+]. The studies reveal that for both skeletal and cardiac R yRs, heterogeneous populations of channels exist, rather than a unifor m behavior. Skeletal muscle RyRs displayed two extremes of behavior: 1 ) low-activity RyRs (LA skeletal RyRs, similar to 35% of the channels) had very low open probability (P-o < 0.1) at all [Ca2+] and remained closed in the presence of Mg2+ (2 mM) and ATP (1 mM); 2) high-activity RyRs (HA skeletal RyRs) had much higher activity and displayed furthe r heterogeneity in their P-o values at low [Ca2+] (<50 nM), and in the ir patterns of activation by [Ca2+]. Hill coefficients for activation (n(H)(a)) varied from 0.8 to 5.2. Cardiac RyRs, in comparison, behaved more homogeneously. Most cardiac RyRs were closed at 100 nM [Ca2+] an d activated in a cooperative manner (n(H)(a) ranged from 1.6 to 5.0), reaching a high P-o (>0.6) in the presence and absence of Mg2+ and ATP . Heart RyRs were much less sensitive (10X) to inhibition by [Ca2+] th an skeletal RyRs. The differential heterogeneity of heart versus skele tal muscle RyRs may reflect the modulation required for calcium-induce d calcium release versus depolarization-induced Ca2+ release.