CALCIUM-INDUCED RELEASE OF STRONTIUM IONS FROM THE SARCOPLASMIC-RETICULUM OF RAT CARDIAC VENTRICULAR MYOCYTES

1. The effects of strontium ions, Sr2+, On Ca2+-dependent feedback mec hanisms during excitation-contraction coupling were examined in voltag e-clamped mt ventricular myocytes in which intracellular [Ca2+] and [S r2+] were monitored with the fluorescent indicator, indo-1. 2. Voltage clamp depolarizations and caffeine applications during superfusion in Ca2+-free, Sr2+- containing solutions were employed to exchange intra cellular Ca2+ with Sr2+. Myocytes were loaded with Sr2+ by applying vo ltage clamp depolarizations during superfusion in Na+-free, Sr2+-conta ining solutions. 3. Caffeine applications produced large fluorescence transients in Sr2+-loaded cells. Thus, Sr2+ could be sequestered and r eleased from the sarcoplasmic reticulum. 4. Ca2+ influx, but not Sr2influx, via sarcolemmal Ca2+ channels evoked ryanodine-sensitive fluor escence transients in Sr2+-loaded cells. These results demonstrated th at Ca2+ influx-induced Sr2+ release (CISR) from the sarcoplasmic retic ulum occurred in these experiments, even though Sr2+ influx-induced Sr 2+ release was not observed. 5. The amplitude of the Ca2+ influx-induc ed fluorescence transient was 17 +/- 1% of the caffeine-induced transi ent (n = 5 cells), an indication that fractional utilization of Sr2+ s equestered in the sarcoplasmic reticulum during CISR was low 6. With i ncreased Sr2+ loading, the amplitude of Ca2+ influx-and caffeine-induc ed fluorescence transients increased, but fractional utilization of sa rcoplasmic reticulum divalent cation stores was independent of the deg ree of Sr2+ loading. These data suggest that Ca2+ influx directly acti vated the release of divalent cations from the sarcoplasmic reticulum, but mechanisms promoting positive feedback of Sr2+ release were minim al during CISR. 7. By comparison, in Ca2+-loaded myocytes, Ca2+ influx -induced Ca2+ release (CICR) utilized a greater fraction of caffeine-r eleasable stores than CISR. Fractional utilization of Ca2+ stores duri ng CICR increased with the degree of Ca2+ loading. 8. Taken together, these results suggest that Ca2+-dependent feedback mechanisms play a m ajor role in determining the extent of sarcoplasmic reticulum Ca2+ rel ease during cardiac excitation-contraction coupling under a wide range of conditions.