English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Neurons in the external segment of the globus pallidus (GPe) are autonomous pacemakers that are capable of sustained fast spiking. The cellular and molecular determinants of pacemaking and fast spiking in GPe neurons are not fully understood, but voltage-dependent Na+ channels must play an important role. Electrophysiological studies of these neurons revealed that macroscopic activation and inactivation kinetics of their Na+ channels were similar to those found in neurons lacking either autonomous activity or the capacity for fast spiking. What was distinctive about GPe Na+ channels was a prominent resurgent gating mode. This mode was significantly reduced in GPe neurons lacking functional Nav1.6 channels. In these Nav1.6 null neurons, pacemaking and the capacity for fast spiking were impaired, as was the ability to follow stimulation frequencies used to treat Parkinson's disease (PD). Simulations incorporating Na+ channel models with and without prominent resurgent gating suggested that resurgence was critical to fast spiking but not to pacemaking, which appeared to be dependent on the positioning of Na+ channels in spike-initiating regions of the cell. These studies not only shed new light on the mechanisms underlying spiking in GPe neurons but also suggest that electrical stimulation therapies in PD are unlikely to functionally inactivate neurons possessing Nav1.6 Na+ channels with prominent resurgent gating.

Nav1.6 Sodium Channels Are Critical to Pacemaking and Fast Spiking in Globus Pallidus Neurons