Related Experiment Video

Updated: Aug 8, 2026

Pull-down of Calmodulin-binding Proteins
07:51

Pull-down of Calmodulin-binding Proteins

Published on: January 23, 2012

Inhibition of calcium-dependent NMDA receptor current rundown by calbindin-D28k

C J Price1, G L Rintoul, K G Baimbridge

  • 1Department of Psychiatry, University of British Columbia, Vancouver, Canada.

Journal of Neurochemistry
|February 4, 1999
PubMed

Insights

The intracellular calcium-binding protein calbindin-D28k does not affect NMDA receptor inactivation but slows calcium-dependent rundown by buffering calcium near the actin cytoskeleton.

Area of Science:

  • Neuroscience
  • Molecular Biology
  • Cell Biology

Background:

  • NMDA receptors are crucial for synaptic plasticity and are regulated by intracellular calcium.
  • Calbindin-D28k is an intracellular calcium-binding protein with a proposed role in calcium buffering.

Purpose of the Study:

  • To investigate whether calbindin-D28k influences the calcium-dependent regulation of NMDA receptor activity.
  • To determine calbindin-D28k's effect on NMDA receptor inactivation, desensitization, and rundown.

Main Methods:

  • Human embryonic kidney 293 cells were co-transfected with NMDA receptor subunits (NR1/NR2A or NR1/NR2B) and calbindin-D28k or beta-galactosidase (control).
  • Nystatin perforated patch-clamp recordings were used to measure NMDA receptor-mediated currents.
  • Calcium-dependent inactivation, desensitization, and rundown of NMDA receptor currents were analyzed.

Main Results:

  • Calbindin-D28k did not alter calcium-dependent inactivation or glycine-independent desensitization of NMDA receptor currents.
  • Calbindin-D28k significantly slowed the development of calcium-dependent rundown of peak glutamate-evoked currents in both NR1/NR2A and NR1/NR2B expressing cells.
  • The inhibitory effect of calbindin-D28k on rundown was more pronounced in NR1/NR2A than NR1/NR2B expressing cells.

Conclusions:

  • Calbindin-D28k does not significantly impact calcium-dependent regulatory processes directly at the NMDA receptor channel.
  • Calbindin-D28k effectively buffers local intracellular calcium elevations, particularly at the actin cytoskeleton, thereby reducing NMDA receptor current rundown.
  • These findings suggest a role for calbindin-D28k in modulating NMDA receptor function through cytoskeletal interactions.

More Related Videos

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate04:48

A High-throughput Calcium-flux Assay to Study NMDA-receptors with Sensitivity to Glycine/D-serine and Glutamate

Published on: July 10, 2018

Horizontal Hippocampal Slices of the Mouse Brain08:59

Horizontal Hippocampal Slices of the Mouse Brain

Published on: September 22, 2020

Related Concept Videos

Long-term Depression01:05

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Long-term Depression01:03

Long-term Depression

Long-term depression, or LTD, is one of the ways by which synaptic plasticity—changes in the strength of chemical synapses—can occur in the brain. LTD is the process of synaptic weakening that occurs over time between pre and postsynaptic neuronal connections. The synaptic weakening of LTD works in opposition to synaptic strengthening by long-term potentiation (LTP) and together are the main mechanisms that underlie learning and memory.
Calcium Ion Concentration Mechanism
If over time, all...
Feedback Regulation of Calcium Concentration01:27

Feedback Regulation of Calcium Concentration

Calcium is an essential signaling molecule required for various cellular functions. Calcium pumps and ion channels on cell and organellar membranes, such as those on the endoplasmic reticulum (ER), regulate calcium concentrations inside the cell. They remain closed, keeping the cytosolic calcium levels low at a resting state.
Various transmembrane receptors, such as G protein-coupled receptors (GPCRs), elicit a response to extracellular signals by increasing cytosolic calcium. Activated GPCRs...
Calmodulin-dependent Signaling01:16

Calmodulin-dependent Signaling

Calmodulin (CaM) is a calcium-binding protein in eukaryotes that controls various calcium-regulated cellular processes. It has four calcium-binding sites that bind calcium to form the calcium-calmodulin ( Ca2+-CaM) complex. GPCR stimulation increases the calcium levels in the cells that bind to CaM and induces a conformational change.
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
Ligand-Gated Ion Channel Receptor: Gating Mechanism01:30

Ligand-Gated Ion Channel Receptor: Gating Mechanism

Ligand-gated ion channels are transmembrane proteins that play a vital role in intercellular communication and functions of the nervous system. They allow the influx of ions across the membrane once the neurotransmitter binds, allowing the subsequent transmission of electrical excitation across the neurons. Other ligand-gated ion channels, like the γ-aminobutyric acid (GABA) receptor, permit anions like chloride into the cells on the binding of the GABA molecule. Their entry into the cell...