Waves of calcium-induced calcium release occur in a variety of cell
types and have been implicated in the origin of cardiac arrhythmias.
We have investigated the effects of inhibiting the SR Ca$^2+$-ATPase
(SERCA) with the reversible inhibitor 2',5'-di(tert-butyl)-1,4-benzohydroquinone
(TBQ) on the properties of these waves. Cardiac myocytes were voltage
clamped at a constant potential between -65 and -40 mV and spontaneous
waves evoked by increasing external Ca$^2+$ concentration to
4 mm. Application of 100 microm TBQ decreased the frequency of waves.
This was associated with increases of resting Ca$^2+$(i), the
time constant of decay of Ca$^2+$(i) and the integral of the
accompanying Na$^+$-Ca$^2+$ exchange current. There was also
a decrease in propagation velocity of the waves. There was an increase
of the calculated Ca$^2+$ efflux per wave. The SR Ca$^2+$
content when a wave was about to propagate decreased to 91.7 +/-
3.2\%. The period between waves increased in direct proportion to
the Ca$^2+$ efflux per wave meaning that TBQ had no effect on
the Ca$^2+$ efflux per unit time. We conclude that (i) decreased
wave frequency is not a direct consequence of decreased Ca$^2+$
pumping by SERCA between waves but, rather, to more Ca$^2+$ loss
on each wave; (ii) inhibiting SERCA increases the chance of spontaneous
Ca$^2+$ release propagating at a given SR content.