Usage Information
Abstract
The hypothesized cellular and molecular mechanisms underlying dystonia are broad and include mutations that perturb Ca2+ signaling, including those affecting voltage gated calcium channels (VGCC). In mice, pharmacological activation of neuronal L-type VGCCs induces dystonia in a dose dependent manner. Here we demonstrate that mice expressing a gain-of-function mutation in the L-type VGCC CaV1.2, associated with Timothy syndrome (TS), exhibit motor dysfunction consistent with dystonia. Although CaV1.2 is broadly expressed throughout peripheral tissues and across the brain, we establish that the dystonia-like behavior is driven by neuronal expression of the mutant calcium channel and observe an associated potential excitatory/inhibitory (E/I) imbalance. Because patients with TS have profound metabolic dysregulation, which is associated with some dystonias, we measured changes in circulating metabolites. The dystonia-like events are sensitive to perturbations in pyruvate metabolism, reminiscent of a subset of dystonias associated with pyruvate dysregulation. Our study provides insight into the potential convergence of previously established causes of dystonia, calcium signaling and metabolic homeostasis.
Authors
Patrick Towers, Hong-Gang Wang, Maiko Matsui, Geoffrey S. Pitt
Usage data is cumulative from October 2026 through October 2026.
| Usage | JCI | PMC |
|---|---|---|
| Text version | 96 | 0 |
| 49 | 0 | |
| Supplemental data | 62 | 0 |
| Citation downloads | 67 | 0 |
| Totals | 274 | 0 |
| Total Views | 274 | |
Usage information is collected from two different sources: this site (JCI) and Pubmed Central (PMC). JCI information (compiled daily) shows human readership based on methods we employ to screen out robotic usage. PMC information (aggregated monthly) is also similarly screened of robotic usage.
Various methods are used to distinguish robotic usage. For example, Google automatically scans articles to add to its search index and identifies itself as robotic; other services might not clearly identify themselves as robotic, or they are new or unknown as robotic. Because this activity can be misinterpreted as human readership, data may be re-processed periodically to reflect an improved understanding of robotic activity. Because of these factors, readers should consider usage information illustrative but subject to change.
