Ci. Spencer et Jr. Berlin, CALCIUM-INDUCED RELEASE OF STRONTIUM IONS FROM THE SARCOPLASMIC-RETICULUM OF RAT CARDIAC VENTRICULAR MYOCYTES, Journal of physiology, 504(3), 1997, pp. 565-578
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.