Voltage-independent changes in L-type Ca2+ current uncoupled from SR Ca2+ release in cardiac myocytes

Laboratory of Cardiovascular Science, Gerontology Research Center, National Institute on Aging, Intramural Research Program, National Institutes of Health, Baltimore, Maryland 21224 To determine the effect of voltage-independent alterations of L-type Ca 2+ current ( I Ca ) on the sarcoplasmic reticular (SR) Ca 2+ release in cardiac myocytes, we measured I Ca and cytosolic Ca 2+ transients (Ca i 2+ ; intracellular Ca 2+ concentration) in voltage-clamped rat ventricular myocytes during 1 ) an abrupt increase of extracellular [Ca 2+ ] (Ca o 2+ ) or 2 ) application of 1 µM FPL-64176, a Ca 2+ channel agonist, to selectively alter I Ca in the absence of changes in SR Ca 2+ loading. On the first depolarization in higher Ca o 2+ , peak I Ca was increased by 46 ± 6% ( P