TY - JOUR
T1 - Distinct patterns of calcium transients during early and delayed afterdepolarizations induced by isoproterenol in ventricular myocytes
AU - De Ferrari, G. M.
AU - Viola, M.
AU - D'Amato, E.
AU - Antolini, R.
AU - Forti, S.
PY - 1995
Y1 - 1995
N2 - Background: The relation between early afterdepolarizations (EADs) and changes in intracellular Ca2+ concentration ([Ca2+]) is still unclear. In the present study, we compared spatiotemporal changes in [Ca2+](i) related to EADs and delayed afterdepolarizations (DADs) induced by isoproterenol. Methods and Results: Isolated patch-clamped guinea pig ventricular myocytes, loaded with fluo-3 acetoxymethyl ester (fluo-3 AM), were paced at 0.1 to 2 Hz. Isoproterenol (100 nmol/L) caused alterations in both phase 2 and phase 4 of the action potential (AP), consistent with EADs and DADs, respectively. During EADs (n=16), similar to driven APs, increases in [Ca2+](i), occurred simultaneously throughout the cell, whereas during DADs (n=25), they originated in discrete cell sites and propagated as a wave. This difference was confirmed by analysis of eight EADs and DADs coupled to the same beat. Ca2+ transients linked to EADs reached a peak relative fluorescence level (expressed as percentage of the maximal level reached during the last stimulated beat) that was always higher than that reached during the DADs (77±3% versus 64±2%, P2+ transients was assessed by the maximal time interval between peaks monitored in different cell regions; this time lag was always greater during DADs than during EADs (290 versus 40 milliseconds, P=.006). Conclusions: The present study had two main findings. First, even very modest notches occurring during the plateau of the AP may be accompanied by a marked secondary increase in [Ca2+](i). Second, these Ca2+ transients occurring during EADs are synchronous throughout the cell and differ significantly from those observed under identical conditions during DADs.
AB - Background: The relation between early afterdepolarizations (EADs) and changes in intracellular Ca2+ concentration ([Ca2+]) is still unclear. In the present study, we compared spatiotemporal changes in [Ca2+](i) related to EADs and delayed afterdepolarizations (DADs) induced by isoproterenol. Methods and Results: Isolated patch-clamped guinea pig ventricular myocytes, loaded with fluo-3 acetoxymethyl ester (fluo-3 AM), were paced at 0.1 to 2 Hz. Isoproterenol (100 nmol/L) caused alterations in both phase 2 and phase 4 of the action potential (AP), consistent with EADs and DADs, respectively. During EADs (n=16), similar to driven APs, increases in [Ca2+](i), occurred simultaneously throughout the cell, whereas during DADs (n=25), they originated in discrete cell sites and propagated as a wave. This difference was confirmed by analysis of eight EADs and DADs coupled to the same beat. Ca2+ transients linked to EADs reached a peak relative fluorescence level (expressed as percentage of the maximal level reached during the last stimulated beat) that was always higher than that reached during the DADs (77±3% versus 64±2%, P2+ transients was assessed by the maximal time interval between peaks monitored in different cell regions; this time lag was always greater during DADs than during EADs (290 versus 40 milliseconds, P=.006). Conclusions: The present study had two main findings. First, even very modest notches occurring during the plateau of the AP may be accompanied by a marked secondary increase in [Ca2+](i). Second, these Ca2+ transients occurring during EADs are synchronous throughout the cell and differ significantly from those observed under identical conditions during DADs.
KW - afterdepolarizations
KW - calcium
KW - isoproterenol
KW - myocytes
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M3 - Article
C2 - 7743611
AN - SCOPUS:0029037794
VL - 91
SP - 2510
EP - 2515
JO - Circulation
JF - Circulation
SN - 0009-7322
IS - 10
ER -