Ca2+ entry through Na(+)‐Ca2+ exchange can trigger Ca2+ release from Ca2+ stores in Na(+)‐loaded guinea‐pig coronary myocytes.

1. The ionized cytosolic calcium concentration ([Ca2+]i) was monitored in voltage‐clamped coronary myocytes at 36 degrees C and 2.5 mM [Ca2+]o using the Ca2+ indicator indo‐1. [Ca2+]i was transiently increased by fast application of 10 mM caffeine, and the mechanisms involved in decay of [Ca2+]i were analysed. 2. Resting [Ca2+]i was 166 +/‐ 62 nM (mean +/‐ S.D.). Caffeine increased [Ca2+]i within 1‐2 s to 1618 +/‐ 490 nM. In the continuous presence of caffeine [Ca2+]i fell close to resting values with a half‐decay time of 5.0 +/‐ 1.6 s. Wash‐out of caffeine induced an undershoot of [Ca2+]i to 105 +/‐ 30 nM. When caffeine was applied repetitively the [Ca2+]i transients were of reduced amplitude indicating that the store had lost a part of releasable Ca2+. 3. After a 1 s caffeine application [Ca2+]i decayed with a half‐time of 2.3 +/‐ 0.8 s to the undershoot of 112 +/‐ 57 nM. The decay of [Ca2+]i was largely prevented by 3 mM [La3+]o; after wash‐out of La3+ [Ca2+]i fell to the resting value without an undershoot. The results demonstrate that La(3+)‐sensitive Ca2+ extrusion contributes to the decay of the [Ca2+]i transient and to the undershoot. 4. With 10 mM [Na+]i, sodium removal from the bath incremented [Ca2+]i in three out of ten cells by 71 +/‐ 11 nM; in the other cells [Ca2+]i did not change. In the absence of extracellular sodium the decay of [Ca2+]i after wash‐out of caffeine was not retarded. 5. To stimulate Na(+)‐Ca2+ exchange, cells were dialysed with pipette solution containing 150 mM NaCl. Elevation of [Na+]i had no significant effect on the resting [Ca2+]i (180 +/‐ 47 nM) or on the caffeine‐induced [Ca2+]i transients (peak 1614 +/‐ 530 nM, half‐time of decay 3 s, undershoot 107 +/‐ 40 nM). 6. With 150 mM [Na+]i, sodium removal resulted in an increase of [Ca2+]i, although responses varied in amplitude (from 130 to 2300 nM) and rate of rise. In the absence of sodium [Ca2+]i remained elevated. After a 1 s caffeine application the undershoot of [Ca2+]i was abolished in sodium‐free solution. When caffeine was applied in sodium‐free solution, the [Ca2+]i transient decayed to a sustained level and the following caffeine response was attenuated. 7. With 150 mM [Na+]i, the effects of sodium removal were strongly suppressed by a preceding depletion of the Ca2+ stores with caffeine. Ryanodine pretreatment abolished the caffeine‐induced [Ca2+]i transients and reduced [Ca2+]i response due to sodium removal.(ABSTRACT TRUNCATED AT 400 WORDS)