Caffeine-induced contractions in neonatal and adult rabbit heart

Mature myocardium utilizes Ca²⁺ released by the sarcoplasmic reticulum (SR) for cell contraction. Exogenous caffeine can also trigger SR Ca²⁺ release. In contrast, immature rabbit heart relies on transsarcolemmal calcium influx; the SR appears to have little influence on cell contraction. Accordingly, we hypothesized that neonatal rabbit myocytes lack a functional SR and therefore would have no response to caffeine. Isolated myocytes were electrically stimulated to load the SR with Ca²⁺ and then exposed to a 1 second pulse of 5 mM caffeine. Adult myocytes exhibited a brisk contraction in response to caffeine. However, neonatal myocytes also exhibited a similar, brisk response. Caffeine-induced contractions were not blocked by 5 mM Ni²⁺ (to block sarcolemmal Ca²⁺ channels) or 10 mM EGTA (to chelate extracellular Ca²⁺), implying that the contractions resulted from intracellular Ca²⁺ release. These data indicate that neonatal myocytes, like adult myocytes, are capable of loading and releasing Ca²⁺ from the SR. Therefore the minor role of SR Ca²⁺ release in developing heart may not result from immaturity of the SR, but rather an inadequate mechanism to trigger SR Ca²⁺ release.