Dataset Information

Ca2+ channel nanodomains boost local Ca2+ amplitude.

ABSTRACT: Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and the Ca(2+) signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited Ca(2+)-dependent inactivation of CaV channels as a nanometer-range Ca(2+) indicator specific to active channels. We observed an unexpected and dramatic boost in nanodomain Ca(2+) amplitude, ten-fold higher than predicted on theoretical grounds. Our results uncover a striking feature of CaV nanodomains, as diffusion-restricted environments that amplify small Ca(2+) fluxes into enormous local Ca(2+) concentrations. This Ca(2+) tuning by the physical composition of the nanodomain may represent an energy-efficient means of local amplification that maximizes information signaling capacity, while minimizing global Ca(2+) load.

SUBMITTER: Tadross MR

PROVIDER: S-EPMC3785779 | biostudies-literature | 2013 Sep

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Ca2+ channel nanodomains boost local Ca2+ amplitude.

Tadross Michael R MR Tsien Richard W RW Yue David T DT

Proceedings of the National Academy of Sciences of the United States of America 20130909 39

Local Ca(2+) signals through voltage-gated Ca(2+) channels (CaVs) drive synaptic transmission, neural plasticity, and cardiac contraction. Despite the importance of these events, the fundamental relationship between flux through a single CaV channel and the Ca(2+) signaling concentration within nanometers of its pore has resisted empirical determination, owing to limitations in the spatial resolution and specificity of fluorescence-based Ca(2+) measurements. Here, we exploited Ca(2+)-dependent i ...[more]

PMID: 24019485

Similar Datasets

Project description:Localized changes in myocardial conduction velocity (CV) are pro-arrhythmic, but high-resolution mapping of local CV is not yet possible during clinical electrophysiology procedures. This is in part because measurement of local CV at small spatial scales (1 mm) requires accurate annotation of local activation time (LAT) differences with very high temporal resolution (≤1 ms), beyond that of standard clinical methods. We sought to develop a method for high-resolution measurement of LAT differences and validate against existing techniques. First, we use a simplified theoretical model to identify a quantitative relationship between the LAT difference of a pair of electrodes and the peak amplitude of the bipolar EGM measured between them. This allows LAT differences to be calculated from bipolar EGM peak amplitude, by a novel "Determination of EGM Latencies by Transformation of Amplitude" (DELTA) method. Next, we use simulated EGMs from a computational model to validate this method. With 1 kHz sampling, LAT differences less than 4 ms were more accurately measured with DELTA than by standard LAT annotation (mean error 3.8% vs. 22.9%). In a 1-dimensional and a 2-dimension model, CV calculations were more accurate using LAT differences found by the DELTA method than by standard LAT annotation (by unipolar dV/dt timing). DELTA-derived LAT differences were more accurate than standard LAT annotation in simulated complex fractionated EGMs from a model incorporating fibrosis. Finally, we validated the DELTA method in vivo using 18,740 bipolar EGMs recorded from the left atrium of 10 atrial fibrillation patients undergoing catheter ablation. Using clinical EGMs, there was agreement in LAT differences found by DELTA, standard LAT annotation, and unipolar waveform cross-correlation. These results demonstrate an underlying relationship between a bipolar EGM's peak amplitude and the activation time difference between its two electrodes. Our computational modeling and clinical results suggest this relationship can be leveraged clinically to improve measurement accuracy for small LAT differences, which may improve CV measurement at small spatial scales.

Dataset Information

Ca2+ channel nanodomains boost local Ca2+ amplitude.

Publications

Ca2+ channel nanodomains boost local Ca2+ amplitude.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets