Dataset Information

Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling.

ABSTRACT: Intracellular calcium ([Ca²⁺]_i) oscillation is a fundamental signaling response of cartilage cells under mechanical loading or osmotic stress. Chondrocytes are usually considered as nonexcitable cells with no spontaneous [Ca²⁺]_i signaling. This study proved that chondrocytes can exhibit robust spontaneous [Ca²⁺]_i signaling without explicit external stimuli. The intensity of [Ca²⁺]_i peaks from individual chondrocytes maintain a consistent spatiotemporal pattern, acting as a unique "fingerprint" for each cell. Statistical analysis revealed lognormal distributions of the temporal parameters of [Ca²⁺]_i peaks, as well as strong linear correlations between their means and sds. Based on these statistical findings, we hypothesized that the spontaneous [Ca²⁺]_i peaks may result from an autocatalytic process and that [Ca²⁺]_i oscillation is controlled by a threshold-regulating mechanism. To test these 2 mechanisms, we established a multistage biophysical model by assuming the spontaneous [Ca²⁺]_i signaling of chondrocytes as a combination of deterministic and stochastic processes. The theoretical model successfully explained the lognormal distribution of the temporal parameters and the fingerprint feature of [Ca²⁺]_i peaks. In addition, by using antagonists for 10 pathways, we revealed that the initiation of spontaneous [Ca²⁺]_i peaks in chondrocytes requires the presence of extracellular Ca²⁺, and that the PLC-inositol 1,4,5-trisphosphate pathway, which controls the release of calcium from the endoplasmic reticulum, can affect the initiation of spontaneous [Ca²⁺]_i peaks in chondrocytes. The purinoceptors and transient receptor potential vanilloid 4 channels on the plasma membrane also play key roles in the spontaneous [Ca²⁺]_i signaling of chondrocytes. In contrast, blocking the T-type or L-type voltage-gated calcium channel promoted the spontaneous calcium signaling. This study represents a systematic effort to understand the features and initiation mechanisms of spontaneous [Ca²⁺]_i signaling in chondrocytes, which are critical for chondrocyte mechanobiology.-Zhou, Y., Lv, M., Li, T., Zhang, T., Duncan, R., Wang, L., Lu, X. L. Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling.

SUBMITTER: Zhou Y

PROVIDER: S-EPMC6436646 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:Stretching single ventricular cardiac myocytes has been shown experimentally to activate transmembrane nicotinamide adenine dinucleotide phosphate oxidase type 2 to produce reactive oxygen species (ROS) and increase the Ca2+ spark rate in a process called X-ROS signaling. The increase in Ca2+ spark rate is thought to be due to an increase in ryanodine receptor type 2 (RyR2) open probability by direct oxidation of the RyR2 protein complex. In this article, a computational model is used to examine the regulation of ROS and calcium homeostasis by local, subcellular X-ROS signaling and its role in cardiac excitation-contraction coupling. To this end, a four-state RyR2 model was developed that includes an X-ROS-dependent RyR2 mode switch. When activated, [Ca2+]i-sensitive RyR2 open probability increases, and the Ca2+ spark rate changes in a manner consistent with experimental observations. This, to our knowledge, new model is used to study the transient effects of diastolic stretching and subsequent ROS production on RyR2 open probability, Ca2+ sparks, and the myoplasmic calcium concentration ([Ca2+]i) during excitation-contraction coupling. The model yields several predictions: 1) [ROS] is produced locally near the RyR2 complex during X-ROS signaling and increases by an order of magnitude more than the global ROS signal during myocyte stretching; 2) X-ROS activation just before the action potential, corresponding to ventricular filling during diastole, increases the magnitude of the Ca2+ transient; 3) during prolonged stretching, the X-ROS-induced increase in Ca2+ spark rate is transient, so that long-sustained stretching does not significantly increase sarcoplasmic reticulum Ca2+ leak; and 4) when the chemical reducing capacity of the cell is decreased, activation of X-ROS signaling increases sarcoplasmic reticulum Ca2+ leak and contributes to global oxidative stress, thereby increases the possibility of arrhythmia. The model provides quantitative information not currently obtainable through experimental means and thus provides a framework for future X-ROS signaling experiments.

Dataset Information

Spontaneous calcium signaling of cartilage cells: from spatiotemporal features to biophysical modeling.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets