BayK 8644 increases resting calcium spark frequency in ferret ventricular myocytes

BayK 8644, an L-type Ca²⁺ channel agonist, has been shown to increase sarcoplasmic reticulum (SR) Ca²⁺ release in dog and ferret ventricular muscle. The visualization of local increase in cytosolic Ca²⁺ concentration, called the 'Ca²⁺ spark', has enabled us to investigate the elementary events of the BayK-induced Ca²⁺ release from the SR. In this study, the effects of BayK on twitch Ca²⁺ transients and Ca²⁺ sparks were examined in ferret ventricular myocytes with laser scanning confocal microscopy and a fluorescent calcium indicator, fluo 3. BayK converted the post rest potentiation of twitch Ca²⁺ transients to decay. The Ca²⁺ spark frequency under control conditions was fairly constant during 20 s of rest after interruption of electrical stimulation. BayK (100 nM) increased the spark frequency by 465.7 ± 90.3% of control but did not change the spatial and temporal characteristics of the individual sparks. The increase in spark frequency by BayK was not affected by perfusion with Ca²⁺-free solution, but was suppressed by the addition of nifedipine (10 μM), suggesting that the BayK effects on Ca²⁺ sparks were mediated by the sarcolemmal dihydropyridine (DHP) receptor, but were independent of Ca²⁺ influx. These findings suggest that BayK activates SR Ca²⁺ release at rest through a putative linkage between the sarcolemmal DHP receptor and the SR ryanodine receptor.