Theoretical estimation of the capacity of intracellular calcium stores in the Bergmann glial cell

Abstract

We propose a mathematical model for calcium dynamics ([Ca2+]i) during metabotropic activation of a specialized astrocyte, the cerebellar Bergmann glial cell. The model adequately describes the experimentally observed behaviour of the prototype in response to single and repetitive metabotropic stimuli and to the inhibition of Ca2+ uptake into the store. By means of the model, the capacity of the intracellular calcium store for two types of calcium buffer was estimated. The estimated buffer capacity of the store lies within the following intervals: (0.8-15.5).10-19 mol calmodulin, and (0.6-12.3).10-19 mol calbindin. This result reveals, that, in the store of a small Ca2+-containing compartment optically detected in the Bergmann glial cell process after electrical stimulation of parallel fibres, the amount of releasable Ca2+ does not exceed 25,000 ions. The quantitative estimates were obtained from experimentally based theoretical relationships between the capacity and volume of the store and parameters of the cytoplasmic calcium buffer. In these relationships, the estimated store capacity was proportional to the total buffer concentration, inversely proportional to the constant of buffer affinity for calcium and was smaller for a greater relative store volume.

A Polymorphism in Thrombospondin-1 Associated with Familial Premature Coronary Heart Disease Causes a Local Change in Conformation of the Ca2+-binding Repeats

“…However, the observation that patients with both Ser-700 alleles have significantly lower levels of plasma TSP-1 than control patients (2) suggests that a secretion defect is present in cells that contribute to the pool of plasma TSP-1. The Ca 2ϩ concentration of the ER has been estimated to be ϳ100 -800 M depending upon the cell type and the method of measurement (41)(42)(43). Our fluorescence results demonstrate that the Ser-700 polymorphism causes a local change in conformation at the lower end of this Ca 2ϩ range.…”

Expansion of the calcium hypothesis of brain aging and Alzheimer's disease: minding the store

“…Release of Ca 2+ from these two intracellular channels is regulated in part by the Ca 2+ concentration gradient present between luminal ER Ca 2+ and cytoplasmic Ca 2+ (Alonso et al ., 1999; Kiryushko et al ., 2002; Solovyova et al ., 2002) and is, thus, also dependent on the Ca 2+ ‐refilling function of sarcoplasmic/endoplasmic reticulum Ca 2+ ‐ATPases (SERCA). Sarcoplasmic/endoplasmic reticulum Ca 2+ ‐ATPases maintain the relatively high levels of Ca 2+ in the ER (hundreds of µ m ) that serve CICR, and IICR, and, in the process, contribute to the control and reduction of cytosolic Ca 2+ (Thastrup et al ., 1990; MacLennan et al ., 1997; Mogami et al ., 1998; Meldolesi, 2001; Berridge, 2002; Verkhratsky, 2004).…”

Glial calcium signaling in physiology and pathophysiology1

“…The excitability of the endomembrane is determined by a specific complement of intracellular Ca 2+ channels and endo(sarco)plasmic reticulum calcium ATP-ases (SERCA), which act as Ca 2+ pumps that transport Ca 2+ against the steep concentration gradient from the cytosol into the ER lumen [17] . The intra-ER free Ca 2+ concentration (or intraluminal Ca 2+ concentration, [Ca 2+ ] L ) reaches several hundreds of micromoles and creates an electro-driving force aimed at the cytosol [18][19][20] . Intracellular Ca 2+ channels residing in the endomembrane are represented by several families: (1) ryanodine receptors (RyRs) directly controlled by cytosolic Ca 2+ ; (2) inositol-1,4,5-trisphosphate receptors (InsP 3 Rs), sensitive to both cytosolic Ca 2+ and second messenger InsP 3 ; and (3) possibly NAADP receptors [21][22][23] .…”

“…The excitability of the endomembrane is determined by a specific complement of intracellular Ca 2+ channels and endo(sarco)plasmic reticulum calcium ATPases (SERCA), which act as Ca 2+ pumps that transport Ca 2+ against the steep concentration gradient from the cytosol into the ER lumen [17] . ] L ) reaches several hundreds of micromoles and creates an electro-driving force aimed at the cytosol [18][19][20] . Intracellular Ca 2+ channels residing in the endomembrane are represented by several families: (1) ] L slows down the SERCA pumping and increases the sensitivity of Ca 2+ release channels to stimulation [24,25] .…”