Our object was to assess the relative roles of transsarcolemmal calcium entry and intracellular calcium release in the contraction of cardiac Purkinje fibers. We observed intracellular calcium transients, membrane potential, and contraction in aequorin-injected canine cardiac Purkinje fibers exposed to highly selective pharmacological modifiers of excitation-contraction coupling. To influence selectively the release of calcium from the sarcoplasmic reticulum, we used the plant alkaloid, ryanodine. To influence calcium entry, selectively, we used either the calcium channel antagonist, nitrendipine, or the calcium channel agonist, Bay k 8644. Ryanodine alone (1μM) reduced both components of the intracellular aequorin luminescence signal (L1 and L2). In three muscles, the luminescence signals were 3% of control in amplitude (standard error of the mean, 2%) without two distinct components and the twitch tension was 2% of control (standard error of the mean, 3%), whereas the action potential was prolonged. The aequorin signal and twitch remaining in ryanodine were abolished by the calcium antagonist nitrendipine (10 μM), which also lowered the action potential plateau, consistent with the block of functional calcium channels. In two experiments, the calcium-channel agonist, Bay k 8644, in the presence of ryanodine, increased the aequorin luminescence and the contraction, but only to a very small fraction of their control values. Sodium withdrawal in potassium-free, ryanodine-containing solution produced large slow increases in calcium and tension, showing that tension could still be produced, that aequorin remained functional, and that sodium/calcium exchange was not inhibited by ryanodine. Caffeine increased intracellular calcium, showing that calcium stores were not depleted. In summary, the negative inotropic effect of ryanodine is due to a decrease in the calcium released from internal stores, and calcium entry normally contributes only a very small fraction of the total activator calcium.
|Original language||English (US)|
|Number of pages||6|
|State||Published - 1985|
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine