Apr 13, 1999

BAY K 8644 modifies Ca2+ cross signaling between DHP and ryanodine receptors in rat ventricular myocytes

The American Journal of Physiology
S Adachi-AkahaneM Morad

Abstract

The amplification factor of dihydropyridine (DHP)/ryanodine receptors was defined as the amount of Ca2+ released from the sarcoplasmic reticulum (SR) relative to the influx of Ca2+ through L-type Ca2+ channels in rat ventricular myocytes. The amplification factor showed steep voltage dependence at potentials negative to -10 mV but was less dependent on voltage at potentials positive to this value. In cells dialyzed with 0.2 mM cAMP in addition to 2 mM fura 2, the Ca2+-channel agonist (-)-BAY K 8644 enhanced Ca2+-channel current (ICa), shifted the activation curve by -10 mV, and significantly delayed its inactivation. Surprisingly, BAY K 8644 reduced the amplification factor by 50% at all potentials, even though the caffeine-releasable Ca2+ stores were mostly intact at holding potentials of -90 mV. In contrast, brief elevation of extracellular Ca2+ activity from 2 to 10 mM enhanced both ICa and intracellular Ca2+ transients in the absence or presence of BAY K 8644 but had no significant effect on the amplification factor. BAY K 8644 abolished the direct dependence of the rate of inactivation of ICa on the release of Ca2+ from the SR. These findings suggest that the gain of the Ca2+-induced Ca2+ release in cardiac myocytes is reg...Continue Reading

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Citations

Mentioned in this Paper

DRUG Screen Quant Caffeine
Ryanodine Receptor 3
Extracellular
Calcium
Left Ventricular Structure
Muscle Cells
Bay-K-8644, (-)-Isomer
Exogenous Calcium Channel Agonists
Bay-K-8644
Protoplasm

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