Related Experiment Video
Updated: Jul 16, 2026
09:30
Assessment of Long-term Depression Induction in Adult Cerebellar Slices
Published on: October 16, 2019
Junctophilin-mediated channel crosstalk essential for cerebellar synaptic plasticity
Sho Kakizawa1, Yasushi Kishimoto, Kouichi Hashimoto
1Department of Pharmacology, Graduate School of Medicine, The University of Tokyo, Tokyo, Japan.
The EMBO Journal
|March 10, 2007
Summary
Junctophilins (JPs) enable communication between ion channels in cerebellar Purkinje cells, essential for motor control. Their absence disrupts this crosstalk, impairing motor learning and coordination.
Area of Science:
- Neuroscience
- Cell Biology
- Ion Channel Physiology
Background:
- Functional crosstalk between cell-surface and intracellular ion channels is crucial for excitable cells.
- Junphilin proteins (JPs) provide structural support for channel crosstalk in muscle cells.
Purpose of the Study:
- To investigate a novel form of ion channel crosstalk in cerebellar Purkinje cells (PCs).
- To determine the role of junctophilins (JPs) in regulating PC excitability and cerebellar function.
Main Methods:
- Utilized mutant mice lacking neural junctin subtypes (JP-DKO).
- Assessed slow afterhyperpolarization (sAHP) generation in PCs.
- Examined long-term depression (LTD) at parallel fiber-PC synapses.
- Evaluated motor coordination and learning in mice.
Main Results:
- sAHP generation in PCs requires ryanodine receptor (RyR)-mediated Ca(2+) release and SK channel activation.
- sAHP was abolished in JP-DKO mice, despite normal channel expression.
- Restoration of JPs or enhanced SK channel activation rescued the sAHP defect.
- JP-DKO mice showed impaired motor coordination and learning, with aberrant synaptic plasticity.
Conclusions:
- JPs mediate Ca(2+)-dependent communication between voltage-gated Ca(2+) channels, RyRs, and SK channels in PCs.
- This JP-supported crosstalk is fundamental for PC excitability, cerebellar LTD, and motor functions.
- Deficiency in JPs leads to impaired cerebellar-dependent motor behaviors.
Related Concept Videos
01:29Excitatory and Inhibitory Effects of Neurotransmitters
When an action potential reaches the presynaptic axon terminal, it releases neurotransmitters from the neuron into the synaptic cleft at a chemical synapse. The released neurotransmitter can be excitatory or inhibitory. The critical criteria commonly used to determine whether a molecule is a neurotransmitter at a chemical synapse are the molecule's presence in the presynaptic neuron. Second, its release is in response to strong presynaptic depolarization. And lastly, the presence of specific...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:26Chemical Synapses
Chemical synapses are specialized sites between two neurons or between a neuron and a non-neuronal cell like a muscle, glandular or sensory cell.
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
Because chemical synapses depend on the release of neurotransmitter molecules from synaptic vesicles to pass on their signal, there is an approximately one millisecond delay between when the axon potential reaches the presynaptic terminal and when the neurotransmitter leads to opening of postsynaptic ion channels. Additionally, this signaling is...
01:20Antiepileptic Drugs: Modulators of Neurotransmitter Release Mediated by SV2A Protein
Antiepileptic drugs, such as levetiracetam (Keppra) and brivaracetam (Briviact), have emerged as crucial tools in managing epilepsy. These medications exert their therapeutic effects by targeting the synaptic vesicle protein SV2A, a transmembrane glycoprotein primarily found in the brain.
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
SV2A is a transmembrane glycoprotein located predominantly in the brain, modulating the release of neurotransmitters for neuronal communication. Both levetiracetam and brivaracetam exhibit a high affinity for...
01:16Calmodulin-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,...
The Ca2+-CaM complex does not have enzymatic activity by itself. Instead, the complex binds downstream target proteins, including membrane proteins or enzymes,...
01:30Ligand-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...