Eg. Lakatta et T. Guarnieri, SPONTANEOUS MYOCARDIAL CALCIUM OSCILLATIONS - ARE THEY LINKED TO VENTRICULAR-FIBRILLATION, Journal of cardiovascular electrophysiology, 4(4), 1993, pp. 473-489
The physiological oscillation of cytosolic [Ca2+] that underlies each
heart beat is generated by the sarcoplasmic reticulum (SR) in response
to an actin potential (AP) and occurs relatively synchronously within
and among cells. When the myocardial cell and SR Ca2+ loading become
sufficiently high, the SR can also generate spontaneous, i.e., not tri
ggered by sarcolemmal depolarization, Ca2+ oscillations (S-CaOs). The
purpose of this review is to describe properties of S-CaOs in individu
al cells, myocardial tissue, and the intact heart, and to examine the
evidence that may link S-CaOs to the initiation or maintenance of vent
ricular fibrillation (VF). The SR Ca2-release that generates S-CaOs oc
curs locally within cells and spreads within the cell via Ca2+ induced
Ca2+ release. The localized increase in cytosolic [Ca2+] due to S-CaO
s may equal that induced by an AP and causes oscillatory sarcolemmal d
epolarizations of cells in which it occurs. These oscillatory depolari
zations are due to Ca2+ activation of the Na/Ca exchanger and of nonsp
ecific cation channels. Asynchronous occurrence of diastolic S-CaOs am
ong cells within the myocardium causes inhomogeneity of diastolic SR C
a2+ loading; this leads to inhomogeneity of the systolic cytosolic [Ca
2+] transient levels in response to a subsequent AP, which leads to he
terogeneity of AP repolarization, due to heterogeneous Ca2+ modulation
of the Na/Ca exchanger, nonspecific cation channels, and of the L-typ
e Ca2+ channel. In a tissue in which asynchronous S-CaOs am occurring
in diastole, the subsequent AP temporarily synchronizes SR Ca2+ loadin
g and release within and among cells. Varying extents of synchronized
S-CaOs then begin to occur during the subsequent diastole. The partial
synchronization of this diastolic S-CaOs cells within myocardial tiss
ue produces aftercontractions and diastolic depolarizations. When S-Ca
Os are sufficiently synchronized, the resultant depolarizations summat
e and can be sufficient to trigger a spontaneous AP. S-CaOs occurrence
within some cells during a long AP plateau also modulates the removal
of voltage inactivation of L-type Ca2+ channels and increases the lik
elihood for ''early after depolarizations'' to occur in myocardial tis
sue. S-CaOs have an apparent modulatory role in the initiation of VF i
n the Ca2+ overload model and in the reflow period following ischemia.
Likewise, in non-a priori Ca2+ overloaded hearts, S-CaOs modulate die
threshold for VF induction (induced typically by alternating current)
but may not be essential for VF induction. The role of S-CaOs in main
tenance of VF in these VF models is less clear: to date there is no ev
idence that inhibition of S-CaOs can abolish VF once it has been estab
lished. The precise definition of the role of S-CaOs in the initiation
and mechanisms of VF merits further study.