# Regulation of Kv2 potassium channel diversity and function in brain by electrically silent subunits

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA AT DAVIS · 2021 · $431,750

## Abstract

Voltage-gated K+ channels of the Kv2 family (Kv2.1 and 2.2) are highly expressed in brain and have important
and diverse functions in mammalian neurons. First, Kv2 channels play important canonical roles as voltage-activated channels that regulate neuronal action potentials and membrane excitability, and genetic mutations or
targeted deletions of these channels cause hyperactivity and seizures. Second, Kv2 channels are highly
clustered on neuronal cell bodies and proximal dendrites and have a separate structural role in organizing
specialized microdomains called endoplasmic reticulum - plasma membrane (ER-PM) junctions, which serve as
important hubs for Ca and lipid signaling in brain neurons. Kv2 channels organize these sites by interacting with
ER VAP proteins via a highly conserved PRC domain in the Kv2 C-terminal tail. Kv2 channels are thought to be
largely composed of Kv2.1 and Kv2.2 subunits, which can co-assemble to form homo- or hetero-tetrameric
channels. Another potential - but largely unexplored - source of Kv2 channel diversity comes from electrically
silent or accessory K+ channel (KvS) subunit genes. This extensive and highly conserved family was termed
“electrically silent” because they require co-assembly together with Kv2.1 or Kv2.2 in order to form functional
ion-conducting channels when expressed in heterologous cells. Gene expression analyses demonstrate that
KvS subunit family members are differentially expressed in distinct brain regions and neuron subtypes, however
there is currently no information available on native KvS-Kv2 channels in brain at the protein level. In preliminary
mass spectrometry-based proteomics experiments, we identified several KvS subunits that interact with Kv2.1
in brain and generated specific antibodies to these subunits. Using these antibodies, we have made the major
discovery that one KvS subunit is a remarkably common constituent of Kv2 channels and that it colocalizes with
Kv2 at ER-PM junctions in subsets of cortical neurons. The objective of this exploratory study, therefore, is to
characterize the neuronal expression and subcellular localization of these KvS family members, and to define
their contribution to Kv2 channel diversity in mammalian brain neurons. This exploratory work will provide
important new insight into how selective expression of KvS subunits impacts Kv2 channel diversity in brain and
how it modulates Kv2 channel function and localization in different neuronal populations.

## Key facts

- **NIH application ID:** 10288261
- **Project number:** 1R21NS123417-01
- **Recipient organization:** UNIVERSITY OF CALIFORNIA AT DAVIS
- **Principal Investigator:** MICHAEL J FERNS
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $431,750
- **Award type:** 1
- **Project period:** 2021-07-01 → 2023-12-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10288261

## Citation

> US National Institutes of Health, RePORTER application 10288261, Regulation of Kv2 potassium channel diversity and function in brain by electrically silent subunits (1R21NS123417-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10288261. Licensed CC0.

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