Calcium transients caused by calcium entry are influenced by the sarcoplasmic reticulum in guinea‐pig atrial myocytes.

1. Single atrial myocytes obtained by enzyme perfusion from hearts of adult guinea‐pigs were investigated using whole‐cell voltage clamp and Indo‐1 micro‐fluorometry. 2. In myocytes loaded with a solution containing citrate as a low‐affinity, non‐saturable Ca2+ chelator, two types of [Ca2+]i transients could be recorded during repetitive activation of L‐type Ca2+ current. Both large and small [Ca2+]i transients occurred; large transients reached peak values of about 1 microM, and small transients were about 100 nM or less in amplitude. 3. In the case of the large transients, peak [Ca2+]i was usually reached with a variable delay after repolarization from a voltage step that activated calcium current (ICa). For the small transients the rise in [Ca2+]i paralleled ICa. Upon repolarization [Ca2+]i started to decay. 4. The small transients reflect entry of Ca2+ through Ca2+ channels (entry transients), whereas the large transients are due to entry and release from the sarcoplasmic reticulum (release transients). 5. The entry transients displayed a positive staircase pattern during trains of depolarizing voltage steps despite constant or even decreasing amplitude of ICa. The steepness of the staircase was increased by elevation of [Ca2+]o. Entry transients were always smallest immediately after a release transient. 6. After functional removal of the sarcoplasmic reticulum by caffeine (1‐5 mM) the staircase pattern of the transients reflecting Ca2+ entry was abolished. 7. It is concluded that the staircase pattern is due to rapid uptake by the sarcoplasmic reticulum of Ca2+ entering the cell, resulting in an attenuation of the signal. The attenuation is strongest shortly after a release signal, when the rate of sequestration of Ca2+ by the SR should be highest. 8. Evidence is provided that a compartment of the SR is involved in attenuation of the entry transients. This compartment has been identified recently as a peripheral release compartment.