The presence and physiological role of Ca2+-induced Ca2+ release (CICR) in nonmuscle excitable cells has been investigated only indirectly through measurements of cytosolic [Ca2+] ([Ca2+]c). Using targeted aequorin, we have directly monitored [Ca2+] changes inside the ER ([Ca2+]ER) in bovine adrenal chromaffin cells. Ca2+ entry induced by cell depolarization triggered a transient Ca2+ release f...

To examine the role of Ca2+ in early neuronal death, we studied the impact of free intracellular calcium concentration ([Ca2+]i) on survivability in populations of cultured mouse spinal neurons. We asked whether early neurotoxicity was triggered by Ca2+ influx, whether elevated [Ca2+]i was a predictive indicator of impending neuronal death, and whether factors other than [Ca2+]i increases influ...

We studied how mitochondrial Ca2+ transport influences [Ca2+](i) dynamics in sympathetic neurons. Cells were treated with thapsigargin to inhibit Ca2+ accumulation by SERCA pumps and depolarized to elevate [Ca2+(i); the recovery that followed repolarization was then examined. The total Ca2+ flux responsible for the [Ca2+](i) recovery was separated into mitochondrial and nonmitochondrial compone...

Rate equations for mitochondrial Ca2+ uptake and release and plasma membrane Ca2+ transport were determined from the measured fluxes in the preceding study and incorporated into a model of Ca2+ dynamics. It was asked if the measured fluxes are sufficient to account for the [Ca2+]i recovery kinetics after depolarization-evoked [Ca2+]i elevations. Ca2+ transport across the plasma membrane was des...

Cellular Ca2+ buffers determine amplitude and diffusional spread of neuronal Ca2+ signals. Fixed Ca2+ buffers tend to retard the signal and to lower the apparent diffusion coefficient (D(app)) of Ca2+, whereas mobile buffers contribute to Ca2+ redistribution. To estimate the impact of the expression of specific Ca2+-binding proteins or the errors in Ca2+ measurement introduced by indicator dyes...

In brain ischemia, gating of postsynaptic glutamate receptors and other membrane channels triggers intracellular Ca2+ overload and cell death. In excitotoxic settings, the initial Ca2+ influx through glutamate receptors is followed by a second uncontrolled Ca2+ increase that leads to neuronal demise. Here we report that the major plasma membrane Ca2+ extruding system, the Na+/Ca2+ exchanger (NC...

The stimulation of cells with agonists that activate phospholipase C, and hence increase the cytoplasmic concentration of inositol 1,4,5-trisphosphate (IP3), often produces complex intracellular Ca2+ signals, such as Ca2+ waves [1]. The key to understanding how Ca2+ waves propagate was the observation that the Ca2+ wave velocity and concentration gradient was maintained as the Ca2+ waves swept ...

The cytosolic free calcium concentration, [Ca2+]i in phagocytic cells (e.g. neutrophils, human leukemic cell line HL-60) is an important determinant of cellular activity. In resting phagocytes [Ca2+]i is low (approximately 100 nM), but in response to occupation of cell surface receptors, it rises to micromolar levels, thereby activating a variety of cellular functions. The increases in [Ca2+]i ...

PGE2-mediated suppression of T cell proliferation during sepsis could result from altered Ca2+ signaling. The present study evaluated the effects of PGE2 on Ca2+ release from intracellular stores and its influx through the plasma membrane in splenic T cells from Sprague-Dawley rats. Intracellular Ca2+ concentration ([Ca2+]i) responses in individual T cells were assessed using the Ca2+ imaging t...

Cardiovascular disease is the leading cause of death in the diabetic population. However, molecular mechanisms underlying diabetic cardiomyopathy remain unclear. We analyzed Ca2+-induced Ca2+ release and excitation-contraction coupling in db/db obese type 2 diabetic mice and their control littermates. Echocardiography showed a systolic dysfunction in db/db mice. Two-photon microscopy identified...