Effects of caffeine on calcium release from the sarcoplasmic reticulum in frog skeletal muscle fibres.

Abstract

3. The voltage dependence of the peak value ofRrei and of the steady level ofRrei at the end of a 60-120 ms pulse were both shifted towards more negative voltages in caffeine. For relatively small pulses the voltage at which a given release waveform was observed was also shifted to more negative voltages.4. Intramembrane charge movements measured in the same fibres in which the above changes in Rrei were observed showed no significant changes in caffeine.5. In caffeine calcium release continued for many milliseconds after the end of a short (10 ms) pulse. Continued release after a pulse was not observed without caffeine and was probably due to positive feedback of elevated [Ca2+] on calcium release resulting from calcium-induced calcium release in caffeine.6. Intramembrane charge movements after short pulses showed no change in caffeine that could account for the continued calcium release after the pulse.7. Continued release after short pulses in caffeine decreased as the pulse duration was increased and was absent for pulses of 60 ms or longer. Rre, also inactivated during such pulses. 8. Relatively large and long conditioning pulses in caffeine suppressed both the peak Rrei and the continued release after short pulses. Peak release and continued release after short pulses recovered in parallel with increasing recovery time following suppression by a conditioning pulse in caffeine. 9. These results indicate that in the presence of caffeine, charge movement and calcium-induced calcium release both contribute significantly to the activation of

Enhancement of Ca2+ release channel activity by phosphorylation of the skeletal muscle ryanodine receptor

“…Ca" is also maintained at high level for several milliseconds after repolarization under voltage clamp conditions [26,27]. The delay between repolarization and the decay of the Ca*' transient is further accentuated by caffeine [28]. Thus, also the ryanodine receptor phosphorylation -possibly occurring at high sarcoplasmic [Ca*'] (2 10 PM) -can lead to an enhanced channel activity resulting in an increased Ca2' release from SR.…”

A repetitive mode of activation of discrete Ca2+ release events (Ca2+ sparks) in frog skeletal muscle fibres

“…Since the mean interspark interval in a rep_mode train is •100 ms, it is expected that subsequent openings in the train would occur during the steady level of release, after the early peak, which has a half-width of 5-20 ms (Klein et al 1990;Simon et al 1991). We have indicated that rep_mode occurs relatively rarely under the conditions of extremely low availability of voltage sensors.…”

Effects of procaine and caffeine on calcium release from the sarcoplasmic reticulum in frog skeletal muscle.

“…Experiments were carried out on single skeletal muscle fibres dissected from ileofibularis or semitendinosus muscles and mounted in a double Vaseline-gap chamber as described previously (Klein et al 1990). The fibres were stretched to sarcomere lengths of 3 8-42 ,sm to eliminate movement and voltage clamped to a holding potential of -100 mV.…”

“…To investigate the role of CICR in skeletal muscle activation we have previously shown Klein, Simon & Schneider, 1990) that caffeine, a potentiator of CICR (Endo, 1975a(Endo, , b, 1985, can cause skeletal muscle to exhibit [Ca2"] transients with properties suggestive of a regenerative CICR mechanism. In the presence of 0 5 mM-caffeine, the rate of calcium release (Rrei) is increased, the voltage dependence ofrelease is shifted to the left, and the time course of decay of A[Ca2+] after repolarization is slowed.…”