Electrophysiological characterization of a Ca3.2 calcium channel missense variant associated with epilepsy and hearing loss.

T-type calcium channelopathies encompass a group of human disorders either caused or exacerbated by mutations in the genes encoding different T-type calcium channels. Recently, a new heterozygous missense mutation in the CACNA1H gene that encodes the Ca3.2 T-type calcium channel was reported in a patient presenting with epilepsy and hearing loss-apparently the first CACNA1H mutation to be associated with a sensorineural hearing condition.

Screening an In-House Isoquinoline Alkaloids Library for New Blockers of Voltage-Gated Na Channels Using Voltage Sensor Fluorescent Probes: Hits and Biases.

Voltage-gated Na (Na) channels are significant therapeutic targets for the treatment of cardiac and neurological disorders, thus promoting the search for novel Na channel ligands. With the objective of discovering new blockers of Na channel ligands, we screened an In-House vegetal alkaloid library using fluorescence cell-based assays. We screened 62 isoquinoline alkaloids (IA) for their ability to decrease the FRET signal of voltage sensor probes (VSP), which were induced by the activation of Na channels with batrachotoxin (BTX) in GH3b6 cells.

Secretory carrier-associated membrane protein 2 (SCAMP2) regulates cell surface expression of T-type calcium channels.

Low-voltage-activated T-type Ca channels are key regulators of neuronal excitability both in the central and peripheral nervous systems. Therefore, their recruitment at the plasma membrane is critical in determining firing activity patterns of nerve cells. In this study, we report the importance of secretory carrier-associated membrane proteins (SCAMPs) in the trafficking regulation of T-type channels.

Trigeminal neuropathic pain is alleviated by inhibition of Ca3.3 T-type calcium channels in mice.

In this brief report, we demonstrate that the Ca3.3 T-type voltage-gated calcium channel subtype is involved in our FRICT-ION model of chronic trigeminal neuropathic pain. We first showed that the gene encoding Ca3.

Functional identification of potential non-canonical N-glycosylation sites within Ca3.2 T-type calcium channels.

Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-translational modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues within the canonical consensus sequence N-X-S/T that is essential for the expression and function of Ca3.

Selective inhibition of neuronal Ca3.3 T-type calcium channels by TAT-based channel peptide.

Low-voltage-activated Ca3 calcium channels (T-type) play an essential role in the functioning of the nervous system where they support oscillatory activities that relie on several channel molecular determinants that shape their unique gating properties. In a previous study, we documented the important role of the carboxy proximal region in the functioning of Ca3.3 channels.

A potential role for T-type calcium channels in homocysteinemia-induced peripheral neuropathy.

Homocysteinemia is a metabolic condition characterized by abnormally high level of homocysteine in the blood and is considered to be a risk factor for peripheral neuropathy. However, the cellular mechanisms underlying toxic effects of homocysteine on the processing of peripheral nociception have not yet been investigated comprehensively. Here, using a rodent model of experimental homocysteinemia, we report the causal association between homocysteine and the development of mechanical allodynia.

Identification of a molecular gating determinant within the carboxy terminal region of Ca3.3 T-type channels.

The physiological functions controlled by T-type channels are intrinsically dependent on their gating properties, and alteration of T-type channel activity is linked to several human disorders. Therefore, it is essential to develop a clear understanding of the structural determinants responsible for the unique gating features of T-type channels. Here, we have investigated the specific role of the carboxy terminal region by creating a series a deletion constructs expressed in tsA-201 cells and analyzing them by patch clamp electrophysiology.