T-type calcium channels perform crucial physiological roles across a wide spectrum of tissues, spanning both neuronal and non-neuronal system. For instance, they serve as pivotal regulators of neuronal excitability, contribute to cardiac pacemaking, and mediate the secretion of hormones. These functions significantly hinge upon the intricate interplay of T-type channels with interacting proteins that modulate their expression and function at the plasma membrane. In this review, we offer a panoramic exploration of the current knowledge surrounding these T-type channel interactors, and spotlight certain aspects of their potential for drug-based therapeutic intervention.

• Klíčová slova
• Calcium channels, Channelosome, Ion channels, T-type channels,
• MeSH
• blokátory kalciových kanálů MeSH
• neurony metabolismus   MeSH
• vápník * metabolismus   MeSH
• vápníkové kanály - typ T * metabolismus   MeSH
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH
• Názvy látek
• blokátory kalciových kanálů MeSH
• vápník * MeSH
• vápníkové kanály - typ T * MeSH

Missense mutations in the human secretary carrier-associated membrane protein 5 (SCAMP5) cause a variety of neurological disorders including neurodevelopmental delay, epilepsy, and Parkinson's disease. We recently documented the importance of SCAMP2 in the regulation of T-type calcium channel expression in the plasma membrane. Here, we show that similar to SCAMP2, the co-expression of SCAMP5 in tsA-201 cells expressing recombinant Cav3.1, Cav3.2, and Cav3.3 channels nearly abolished whole-cell T-type currents. Recording of intramembrane charge movements revealed that SCAMP5-induced inhibition of T-type currents is primarily caused by the reduced expression of functional channels in the plasma membrane. Moreover, we show that SCAMP5-mediated downregulation of Cav3.2 channels is essentially preserved with disease-causing SCAMP5 R91W and G180W mutations. Hence, this study extends our previous findings with SCAMP2 and indicates that SCAMP5 also contributes to repressing the expression of T-type channels in the plasma membrane.

• Klíčová slova
• Calcium channels, Channelopathy, Ion channels, SCAMP5, Secretory carrier-associated membrane protein 5, T-type channels,
• MeSH
• buněčná membrána MeSH
• down regulace MeSH
• lidé MeSH
• membránové proteiny genetika   MeSH
• mutace MeSH
• vápníkové kanály - typ T * genetika   MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• membránové proteiny MeSH
• SCAMP5 protein, human MeSH Prohlížeč
• vápníkové kanály - typ T * MeSH

Low-voltage-activated T-type Ca2+ 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. We identified SCAMP2 as a novel Cav3.2-interacting protein. In addition, we show that co-expression of SCAMP2 in mammalian cells expressing recombinant Cav3.2 channels caused an almost complete drop of the whole cell T-type current, an effect partly reversed by single amino acid mutations within the conserved cytoplasmic E peptide of SCAMP2. SCAMP2-induced downregulation of T-type currents was also observed in cells expressing Cav3.1 and Cav3.3 channel isoforms. Finally, we show that SCAMP2-mediated knockdown of the T-type conductance is caused by the lack of Cav3.2 expression at the cell surface as evidenced by the concomitant loss of intramembrane charge movement without decrease of total Cav3.2 protein level. Taken together, our results indicate that SCAMP2 plays an important role in the trafficking of Cav3.2 channels at the plasma membrane.

• Klíčová slova
• Calcium channels, Cav3.2 channels, Ion channels, SCAMP2, Secretory carrier-associated membrane protein 2, T-type channels, Trafficking,
• MeSH
• buněčná membrána metabolismus   MeSH
• membránové proteiny metabolismus   MeSH
• neurony metabolismus   MeSH
• savci metabolismus   MeSH
• transportní proteiny metabolismus   MeSH
• vápník metabolismus   MeSH
• vápníkové kanály - typ T * metabolismus   MeSH
• zvířata MeSH
• Check Tag
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• membránové proteiny MeSH
• transportní proteiny MeSH
• vápník MeSH
• vápníkové kanály - typ T * MeSH