Related Experiment Video
Updated: Apr 23, 2026
A Simple and Inexpensive Method for Determining Cold Sensitivity and Adaptation in Mice
Published on: March 17, 2015
Differential contribution of TRPM4 and TRPM5 nonselective cation channels to the slow afterdepolarization in mouse
Ya-Ting Lei1, Sebastien J Thuault1, Pierre Launay2
1Department of Neuroscience, Columbia University Medical Center, New York State Psychiatric Institute New York, NY, USA.
Abstract:
In certain neurons from different brain regions, a brief burst of action potentials can activate a slow afterdepolarization (sADP) in the presence of muscarinic acetylcholine receptor agonists. The sADP, if suprathreshold, can contribute to persistent non-accommodating firing in some of these neurons. Previous studies have characterized a Ca(2+)-activated non-selective cation (CAN) current (ICAN ) that is thought to underlie the sADP. ICAN depends on muscarinic receptor stimulation and exhibits a dependence on neuronal activity, membrane depolarization and Ca(2+)-influx similar to that observed for the sADP. Despite the widespread occurrence of sADPs in neurons throughout the brain, the molecular identity of the ion channels underlying these events, as well as ICAN , remains uncertain. Here we used a combination of genetic, pharmacological and electrophysiological approaches to characterize the molecular mechanisms underlying the muscarinic receptor-dependent sADP in layer 5 pyramidal neurons of mouse prefrontal cortex. First, we confirmed that in the presence of the cholinergic agonist carbachol a brief burst of action potentials triggers a prominent sADP in these neurons. Second, we confirmed that this sADP requires activation of a PLC signaling cascade and intracellular calcium signaling. Third, we obtained direct evidence that the transient receptor potential (TRP) melastatin 5 channel (TRPM5), which is thought to function as a CAN channel in non-neural cells, contributes importantly to the sADP in the layer 5 neurons. In contrast, the closely related TRPM4 channel may play only a minor role in the sADP.
Insights
Researchers identified the Transient Receptor Potential Melastatin 5 (TRPM5) channel as a key player in slow afterdepolarizations (sADPs) in brain neurons. This finding clarifies the molecular basis of neuronal excitability and persistent firing.
Area of Science:
- Neuroscience
- Molecular Biology
- Electrophysiology
Background:
- Slow afterdepolarizations (sADPs) are crucial for neuronal excitability, enabling persistent firing in response to muscarinic acetylcholine receptor agonists.
- The underlying ion channels for sADPs and the associated Ca(2+)-activated non-selective cation (CAN) current (ICAN) remain largely unidentified.
Purpose of the Study:
- To elucidate the molecular identity of the ion channels responsible for muscarinic receptor-dependent sADPs in layer 5 pyramidal neurons of the mouse prefrontal cortex.
Main Methods:
- Genetic, pharmacological, and electrophysiological approaches were employed.
- Experiments involved stimulating neurons with a cholinergic agonist (carbachol) and observing the resulting sADP.
- Investigated the involvement of phospholipase C (PLC) signaling and intracellular calcium.
Main Results:
- Confirmed that carbachol triggers a prominent sADP in layer 5 pyramidal neurons following a burst of action potentials.
- Demonstrated that sADP generation requires PLC and intracellular calcium signaling.
- Provided direct evidence implicating the Transient Receptor Potential Melastatin 5 (TRPM5) channel in the sADP, with TRPM4 playing a minor role.
Conclusions:
- The TRPM5 channel is a significant molecular component underlying the muscarinic receptor-dependent sADP in prefrontal cortex neurons.
- Findings contribute to understanding the molecular mechanisms of neuronal excitability and the generation of persistent firing patterns.
