Dataset Information

High-Frequency Microdomain Ca²⁺ Transients and Waves during Early Myelin Internode Remodeling.

ABSTRACT: Ensheathment of axons by myelin is a highly complex and multi-cellular process. Cytosolic calcium (Ca²⁺) changes in the myelin sheath have been implicated in myelin synthesis, but the source of this Ca²⁺ and the role of neuronal activity is not well understood. Using one-photon Ca²⁺ imaging, we investigated myelin sheath formation in the mouse somatosensory cortex and found a high rate of spontaneous microdomain Ca²⁺ transients and large-amplitude Ca²⁺ waves propagating along the internode. The frequency of Ca²⁺ transients and waves rapidly declines with maturation and reactivates during remyelination. Unexpectedly, myelin microdomain Ca²⁺ transients occur independent of neuronal action potential generation or network activity but are nearly completely abolished when the mitochondrial permeability transition pores are blocked. These findings are supported by the discovery of mitochondria organelles in non-compacted myelin. Together, the results suggest that myelin microdomain Ca²⁺ signals are cell-autonomously driven by high activity of mitochondria during myelin remodeling.

SUBMITTER: Battefeld A

PROVIDER: S-EPMC6316190 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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High-Frequency Microdomain Ca2+ Transients and Waves during Early Myelin Internode Remodeling.

Battefeld Arne A Popovic Marko A MA de Vries Sharon I SI Kole Maarten H P MHP

Cell reports 20190101 1

Ensheathment of axons by myelin is a highly complex and multi-cellular process. Cytosolic calcium (Ca2+) changes in the myelin sheath have been implicated in myelin synthesis, but the source of this Ca2+ and the role of neuronal activity is not well understood. Using one-photon Ca2+ imaging, we investigated myelin sheath formation in the mouse somatosensory cortex and found a high rate of spontaneous microdomain Ca2+ transients and large-amplitude Ca<s ...[more]

PMID: 30605675

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Project description:Myenteric plexus interstitial cells of Cajal (ICC-MY) in the small intestine are Kit+ electrical pacemakers that express the Ano1/TMEM16A Ca2+-activated Cl- channel, whose functions in the gastrointestinal tract remain incompletely understood. In this study, an inducible Cre-LoxP-based approach was used to advance the understanding of Ano1 in ICC-MY of adult mouse small intestine. KitCreERT2/+;Ano1Fl/Fl mice were treated with tamoxifen or vehicle, and small intestines (mucosa free) were examined. Quantitative RT-PCR demonstrated ~50% reduction in Ano1 mRNA in intestines of conditional knockouts (cKOs) compared with vehicle-treated controls. Whole mount immunohistochemistry showed a mosaic/patchy pattern loss of Ano1 protein in ICC networks. Ca2+ transients in ICC-MY network of cKOs displayed reduced duration compared with highly synchronized controls and showed synchronized and desynchronized profiles. When matched, the rank order for Ano1 expression in Ca2+ signal imaged fields of view was as follows: vehicle controls>>>cKO(synchronized)>cKO(desynchronized). Maintenance of Ca2+ transients' synchronicity despite high loss of Ano1 indicates a large functional reserve of Ano1 in the ICC-MY network. Slow waves in cKOs displayed reduced duration and increased inter-slow-wave interval and occurred in regular- and irregular-amplitude oscillating patterns. The latter activity suggested ongoing interaction by independent interacting oscillators. Lack of slow waves and depolarization, previously reported for neonatal constitutive knockouts, were also seen. In summary, Ano1 in adults regulates gastrointestinal function by determining Ca2+ transients and electrical activity depending on the level of Ano1 expression. Partial Ano1 loss results in Ca2+ transients and slow waves displaying reduced duration, while complete and widespread absence of Ano1 in ICC-MY causes lack of slow wave and desynchronized Ca2+ transients.NEW & NOTEWORTHY The Ca2+-activated Cl- channel, Ano1, in interstitial cells of Cajal (ICC) is necessary for normal gastrointestinal motility. We knocked out Ano1 to varying degrees in ICC of adult mice. Partial knockout of Ano1 shortened the widths of electrical slow waves and Ca2+ transients in myenteric ICC but Ca2+ transient synchronicity was preserved. Near-complete knockout was necessary for transient desynchronization and loss of slow waves, indicating a large functional reserve of Ano1 in ICC.

Dataset Information

High-Frequency Microdomain Ca²⁺ Transients and Waves during Early Myelin Internode Remodeling.

Publications

High-Frequency Microdomain Ca<sup>2+</sup> Transients and Waves during Early Myelin Internode Remodeling.

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