Related Experiment Video

Updated: Aug 18, 2026

Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons
06:54

Quantifying Spontaneous Ca2+ Fluxes and their Downstream Effects in Primary Mouse Midbrain Neurons

Published on: September 9, 2020

Effect of L-type calcium channel antagonists on spermine-induced CNS excitation in vivo

Karen M Doyle1, Brian P Kirby, Desiree Murphy

  • 1Department of Pharmacology, School of Pharmacy, Trinity College, Dublin 2, Ireland. karen.doyle@nuigalway.ie

Neuroscience Letters
|May 3, 2005
PubMed

Insights

Certain L-type calcium channel blockers, specifically those targeting the alpha1 subunit, effectively reduced central nervous system (CNS) excitation caused by spermine in mice. Gabapentin did not show this inhibitory effect.

Area of Science:

  • Neuropharmacology
  • Calcium Channel Modulation

Background:

  • Spermine can induce central nervous system (CNS) excitation, leading to tremors and fatal convulsions in mice.
  • L-type calcium channels are implicated in neuronal excitability and may play a role in spermine's neurotoxic effects.

Purpose of the Study:

  • To investigate the efficacy of specific L-type calcium channel antagonists in preventing spermine-induced CNS excitation.
  • To determine if the site of action (alpha1 vs. alpha2delta subunit) influences the inhibitory effect.

Main Methods:

  • Mice were administered an excitotoxic dose of spermine (100 microg, intracerebroventricular).
  • The effects of nitrendipine, nisoldipine, verapamil (L-type calcium channel antagonists acting at alpha1 subunit), and gabapentin (postulated antagonist at alpha2delta subunit) were assessed.
  • Inhibition of spermine-induced CNS excitation, tremor, and convulsions was evaluated.

Main Results:

  • Nitrendipine and nisoldipine significantly inhibited spermine-induced CNS excitation and subsequent convulsions.
  • Verapamil also demonstrated inhibitory effects against spermine-induced CNS excitation.
  • Gabapentin failed to inhibit the development of spermine-induced CNS effects.

Conclusions:

  • Antagonists targeting the alpha1 subunit of L-type calcium channels are effective in inhibiting spermine-induced CNS excitation in vivo.
  • These findings underscore the critical role of alpha1 subunit-mediated L-type calcium channel activity in spermine's neurotoxic actions.

More Related Videos

In Vivo Calcium Imaging in C. elegans Body Wall Muscles08:03

In Vivo Calcium Imaging in C. elegans Body Wall Muscles

Published on: October 20, 2019

Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants18:01

Paradigms for Pharmacological Characterization of C. elegans Synaptic Transmission Mutants

Published on: August 18, 2008

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...
Indirect-Acting Cholinergic Agonists: Pharmacological Actions01:30

Indirect-Acting Cholinergic Agonists: Pharmacological Actions

Indirect-acting cholinergic agonists, also known as anticholinesterases, exert their pharmacological effects by enhancing cholinergic transmission in various body parts, including the neuromuscular junction, autonomic cholinergic synapses, and the brain.
At the neuromuscular junction, these agents work by inhibiting the breakdown of acetylcholine, allowing it to remain bound to the receptor and bind to nearby receptors. This process leads to repetitive firing of the endplate, causing muscle...
Drugs Acting on Autonomic Ganglia: Stimulants01:23

Drugs Acting on Autonomic Ganglia: Stimulants


Ganglionic stimulants activate NM nicotinic receptors in autonomic ganglia, falling into two categories: nicotine mimetics [e.g., lobeline, dimethylpiperazine, tetramethylammonium] and muscarinic receptor agonists [e.g., muscarine, methacholine]. The first category's action is rapid and blocked by nicotinic receptor antagonists, while the second category's action is delayed and blocked by atropine-like agents. Nicotine, an alkaloid, affects the heart rate by stimulating sympathetic or...
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,...