Effects of ryanodine on the action potentials and the ionic currents in spontaneously beating single rabbit sinoatrial (SA) nodal cells were examined using current-clamp and whole-cell voltage-clamp techniques. 2. Cumulative administrations of ryanodine (10(-8) to 10(-4) M) caused a negative chronotropic effect in a concentration-dependent manner; the effect was not modified by atropine (10(-7) M). At 10(-6) M, ryanodine increased the action potential amplitude and the maximum rate of depolarization, and prolonged the duration of action potentials, significantly. The maximum diastolic potential was unaffected. 3. No arrhythmia occurred in the presence of ryanodine (10(-6) M) alone, but addition of either caffeine (10 mM) or high Ca2+ (10.8 mM) elicited arrhythmias. The incidence increased with an increase in extracellular Ca2+ concentration. 4. Ryanodine, at 10(-6) M, enhanced the Ca2+ current but, at 10(-5) M, inhibited it. Ryanodine inhibited the delayed rectifier K+ current and the hyperpolarization-activated inward current in a concentration-dependent manner. 5. In addition, ryanodine actually elevated the cytosolic Ca2+ level in the SA nodal cells loaded with Ca(2+)-sensitive fluorescent dye (fura-2). 6. These results indicate that ryanodine modulates the ionic currents (presumably dependent on cellular Ca2+ concentration), suggesting similar pharmacological properties to caffeine.
