Topic: Cav2.1

Parkinson's disease is a motor and cognitive neurodegenerative disorder associated to the progressive loss of Substantia Nigra pars compacta dopaminergic neurons. One cause of the disease is associated with the spreading of α-synuclein aggregates. Recent findings indicate that extracellular α-synuclein oligomers represent the most neurotoxic species and reduce the firing discharge of midbrain neurons, impair network synchronization, up-regulate Cav2.2 Ca channels and neurotransmitter release in cortical neurons. Here we combined conventional electrophysiology (current-clamp) and diamond multi

The roles of auxiliary α2δ subunits of voltage-gated calcium channels (CaVs) in modulating channel membrane expression and calcium current properties are widely recognized. In addition, recent literature suggests an important role of α2δ proteins in synapse formation, differentiation, and synaptic wiring. Therefore, it is not surprising that α2δ proteins have been linked to neurological, neurodevelopmental, and neuropsychiatric disorders. Genetic variants of the α2δ-2 isoform have been associated with epileptic encephalopathy and cerebellar atrophy. In this study we performed a detailed functi

Cav2.1 channels are critically important for fast synaptic transmission at central synapses. The two Cav2.1 isoforms Cav2.1[EFa] and Cav2.1[EFb] are generated by alternative splicing of two mutually exclusive exons, 37a and 37b. Both isoforms are expressed throughout the adult brain, whereas Cav2.1[EFb] predominates at early stages of development. Cav2.1[EFa] supports synchronous release and short-term synaptic depression, whereas Cav2.1[EFb] boosts asynchronous release and short-term facilitation. We investigated whether the two isoforms were distinctly located at excitatory nerve terminals r

Temporal lobe epilepsy (TLE) is the most common form of focal epilepsy. Though available anticonvulsants achieve a full seizure control for two-thirds of the TLE patients, one third does not respond sufficiently to these drugs and resection of the seizure area is the best possible treatment for them. One way to improve this is to identify key regulatory ion channels in excitatory synaptic function. Here, we investigated the ultrastructural localization of I) P/Q-type voltage-gated calcium channels (Cav2.1) at the presynaptic site triggering vesicle release and II) AMPA receptors mediating the

Voltage-gated CaV2.1 Ca2+ channels play a crucial role in regulating neurotransmitter release, thus contributing to processes such as learning and memory. Despite their recognised importance in neural function, there is limited information on their potential involvement in neurodegenerative conditions such as Alzheimer's disease (AD). Aims: to explore the impact of amyloid-β (Aβ) pathology on the nanoscale compartmentalization of CaV2.1-GABAB in the hippocampus.Methods: We used histoblot and SDS-digested freeze-fracture replica labelling (SDS-FRL) techniques in the CA1 field of the hippocampus

Cortical spreading depression (CSD) is the neurophysiological correlate of migraine aura and a trigger of migraine pain mechanisms. The mechanisms of initiation of CSD in migraineurs are unknown. Insights into these mechanisms can be obtained by studying the mechanisms of facilitation of CSD initiation in genetic mouse models of the disease. Here, we investigated these mechanisms in knock-in mice carrying a mutation in cacna1a causing familial hemiplegic migraine (FHM1 mice). High KCl puffs of increasing duration up to the threshold duration eliciting a CSD were applied on layer 2/3 of cerebra

Studying synaptic proteins, which are regulating synaptic transmission and organization, is a challenging task as traditional localization and staining methods face limitations in mapping proteins in living cells. For example, traditional antibodies are too large to freely diffuse into the extracellular protein-enriched synaptic cleft and the use of detergents for improving cell penetration cannot be applied in living cells and damages synaptic membrane integrity. We are particularly interested in understanding the mechanism of calcium-regulated neurotransmitter release and synapse formation b

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Voltage-gated calcium channels (Cav) mediate calcium influx in living cells and are necessary for essential physiological functions such as muscle contraction and excitation-transcription coupling. Channels of the Cav2 family (Cav2.1, 2.2, and 2.3) are highly expressed in the central nervous system (CNS) and are important regulators of neuronal excitability. They are involved in pre- and postsynaptic functions where they, for example, trigger neurotransmitter release. Cav2.3 (α1E) is involved in neuronal development and, when compared to other α1 subunits, shows the strongest expression in mou

P/Q-type calcium channels, also known as CaV2.1, are voltage-gated Ca2+ channels (VGCCs) enriched at many central synapses where they control neurotransmitter release. Loss-of-function mutations in CACNA1A, the gene encoding the pore-forming α1 subunit of CaV2.1, underlie several neurological disorders, including episodic ataxia type II (EA2) and absence epilepsy.Despite the existence of several experimental models, the etiology of these diseases still remains poorly understood, preventing the development of effective therapeutic strategies.Here, we have developed a CRISPR/Cas9-mediated strate