# Store-Operated Channels in the Nervous System

> **NIH NIH R01** · NORTHWESTERN UNIVERSITY · 2020 · $361,909

## Abstract

Project Abstract
Astrocytes comprise the major cell type in the brain and regulate numerous functions including
neural development, clearance of neurotransmitters, and regulation of blood flow. Recent
evidence indicates that astrocytes also play a direct role in regulating synaptic transmission by
modulating neuronal activity through the secretion of `gliotransmitters' such as glutamate, ATP, and
D-serine. Astrocytes are intimately associated with pre- and post-synaptic neuronal membranes in
an anatomical unit referred to as the tripartite synapse. This close association allows astrocytes to
sense neurotransmitters released by neurons, and conversely communicate with neighboring
neurons through the action of gliotransmitters. Previous studies have suggested that a major
mechanism mediating release of gliotransmitters is vesicular exocytosis evoked by elevations in
intracellular [Ca2+]i. However, the molecules and pathways involved in generating Ca2+ elevations
in astrocytes remain poorly understood. Our preliminary evidence indicates that store-operated
Ca2+ release-activated Ca2+ (CRAC) channels are a major mechanism for neurotransmitter-evoked
Ca2+ signals in astrocytes. We further find that ablation of CRAC channel expression or
pharmacological blockade suppresses gliotransmitter release. Based on this evidence, we
hypothesize that CRAC channels are essential regulators of astrocyte gliotransmitter exocytosis
and the bidirectional communication between neurons and astrocytes at the tripartite synapse. We
propose the three specific aims to test this hypothesis: 1) Define the molecular composition of
CRAC channels in astrocytes and their contribution for the generation of complex astrocyte Ca2+
signals. 2) Determine the role of CRAC channels for secretion of gliotransmitters, and 3) Determine
the role of CRAC channels for astrocyte modulation of synaptic transmission. We will approach
these questions using a multidisciplinary approach that combines genetic knockouts of CRAC
channel proteins with in-depth molecular and biochemical assays, whole-cell and slice
electrophysiological recordings, Ca2+ imaging using wide-field and spinning disk confocal
microscopy, and gliotransmission assays. Collectively, results from these studies will advance our
understanding of the physiological role of CRAC channels for regulating Ca2+ homeostasis and
gliotransmission in astrocytes and aid the quest for developing new therapies for pathological
diseases affecting synaptic function.

## Key facts

- **NIH application ID:** 9841457
- **Project number:** 5R01NS057499-13
- **Recipient organization:** NORTHWESTERN UNIVERSITY
- **Principal Investigator:** Murali Prakriya
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,909
- **Award type:** 5
- **Project period:** 2007-02-13 → 2021-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9841457

## Citation

> US National Institutes of Health, RePORTER application 9841457, Store-Operated Channels in the Nervous System (5R01NS057499-13). Retrieved via AI Analytics 2026-05-27 from https://api.ai-analytics.org/grant/nih/9841457. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*