Related Experiment Video

Updated: Aug 17, 2026

Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells
09:06

Localization of Plasma Membrane and Intracellular Neuronal Nicotinic Acetylcholine Receptors Using Quantitative Imaging in Mammalian Cells

Published on: December 19, 2025

Multiple calcium channels and kinases mediate alpha7 nicotinic receptor neuroprotection in PC12 cells

Ke Ren1, Viviana Puig, Roger L Papke

  • 1Department of Pharmaceutics, University of Florida, Gainesville, Florida 32610, USA.

Journal of Neurochemistry
|June 23, 2005
PubMed

Insights

Alpha7 nicotinic receptors protect cells by regulating intracellular calcium. This neuroprotection involves protein kinase C and ERK1/2 activation, independent of L-type calcium channels.

Area of Science:

  • Neuroscience
  • Pharmacology
  • Cell Biology

Background:

  • Alpha7 nicotinic receptors are calcium-permeable and implicated in neuroprotection.
  • Understanding the downstream signaling pathways is crucial for therapeutic development.

Purpose of the Study:

  • To investigate the role of intracellular calcium and downstream channels in alpha7 nicotinic receptor-mediated neuroprotection.
  • To elucidate the specific signaling molecules and calcium channels involved in this protective mechanism.

Main Methods:

  • Utilized pheochromocytoma cells subjected to neuroprotection assays.
  • Employed the alpha7 agonist GTS-21 and various inhibitors including BAPTA, xestospongin C, U-73122, and PD98059.
  • Assessed cell viability, protein kinase C activation, and ERK1/2, JNK, and p38 phosphorylation.

Main Results:

  • GTS-21 demonstrated neuroprotection against NGF + serum deprivation.
  • This protection was abrogated by the intracellular calcium chelator BAPTA, which also inhibited PKC activation.
  • Inositol triphosphate calcium channels and phospholipase C were implicated, while ryanodine had a partial effect and L-type channels did not.
  • GTS-21 activated ERK1/2, and its inhibition blocked neuroprotection.

Conclusions:

  • Intracellular calcium signaling, PKC, and ERK1/2 pathways are essential for alpha7 nicotinic receptor-mediated neuroprotection.
  • The neuroprotective mechanism does not appear to involve L-type calcium channels.
  • Findings highlight potential therapeutic targets for neurodegenerative conditions.

More Related Videos

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons12:19

Live Imaging of Nicotine Induced Calcium Signaling and Neurotransmitter Release Along Ventral Hippocampal Axons

Published on: June 24, 2015

Related Concept Videos

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...
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,...
G-Protein Gated Ion Channels01:21

G-Protein Gated Ion Channels

GPCRs are primarily responsible for our sense of smell, taste, and vision.  The binding of a sensory stimulus activates GPCR to stimulate effector proteins, many of which are ion channels in the sensory organs. GPCRs modulate the opening and closing of the target ion channels either directly by binding them, or by releasing second messengers that activate these channels. As ions move across the membrane, the membrane potential is altered, which induces an appropriate response.
Sensory organs,...
Cholinergic Receptors: Nicotinic01:15

Cholinergic Receptors: Nicotinic

Nicotinic receptors are ligand-gated ion channels that are activated by acetylcholine and nicotine. Upon activation, they cause a rapid increase in the permeability of cells to K+, Na+, and Ca2+, followed by depolarization and excitation. They are in the autonomic ganglia, skeletal neuromuscular junction, CNS, and adrenal medulla.
There are two types of nicotinic receptors: neuromuscular (NM/NM/N1) and neuronal (NN/NN/N2). The two families differ based on their location and selectivity to...
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...
Cholinergic Receptors: Muscarinic01:25

Cholinergic Receptors: Muscarinic

The pharmacological actions of acetylcholine are elicited via its binding to two families of cholinergic receptors or cholinoceptors, namely, muscarinic and nicotinic receptors. Muscarinic receptors are G protein-coupled receptors and have five subtypes, M1–M5. All mAChR subtypes are activated by acetylcholine and blocked by the antagonist, atropine. 
The subtypes M1, M3, and M5 couple with the Gq subunit and activate the phospholipase C (PLC) activity, mobilizing intracellular Ca2+. Activation...