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+ concent ration, called the ''Ca2+ spark'', has enabled us to investigate the e lementary 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 confo cal microscopy and a fluorescent calcium indicator, flue 3. BayK conve rted the post rest potentiation of twitch Ca2+ transients to decay. Th e Ca2+ spark frequency under control conditions was fairly constant du ring 20s of rest after interruption of electrical stimulation. BayK (1 00 nM) increased the spark frequency by 465.7 +/- 90.3 % of control bu t did not change the spatial and temporal characteristics of the indiv idual sparks. The increase in spark frequency by BayK was not affected by perfusion with Ca2+-free solution, but was suppressed by the addit ion of nifedipine (10 mu M), suggesting that the BayK effects on Ca2sparks were mediated by the sarcolemmal dihydropyridine (DHP) receptor , but were independent of Ca2+ influx. These findings suggest that Bay K activates SR Ca2+ release at rest through a putative linkage between the sarcolemmal DHP receptor and the SR ryanodine receptor.