T-type channels in cancer cells: Driving in reverse
In the strongly polarized membranes of excitable cells, activation of T-type Ca2+ channels (TTCCs) by weak depolarizing stimuli allows the influx of Ca2+ which further amplifies membrane depolarization, thus 'recruiting' higher threshold voltage-gated channels to promote action potential f...
| Autores: | , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2022 |
| País: | España |
| Institución: | Varias* (Consorci de Biblioteques Universitáries de Catalunya, Centre de Serveis Científics i Acadèmics de Catalunya) |
| Repositorio: | Recercat. Dipósit de la Recerca de Catalunya |
| OAI Identifier: | oai:recercat.cat:10459.1/83504 |
| Acceso en línea: | https://doi.org/10.1016/j.ceca.2022.102610 http://hdl.handle.net/10459.1/83504 |
| Access Level: | acceso abierto |
| Palabra clave: | Calcium signaling pathways Calcium-activated potassium channels Cancer cells Feedback loops Membrane potential Proliferation Survival T-type calcium channels |
| Sumario: | In the strongly polarized membranes of excitable cells, activation of T-type Ca2+ channels (TTCCs) by weak depolarizing stimuli allows the influx of Ca2+ which further amplifies membrane depolarization, thus 'recruiting' higher threshold voltage-gated channels to promote action potential firing. Nonetheless, TTCCs perform other functions in the plasma membrane of both excitable and non-excitable cells, in which they regulate a number of biochemical pathways relevant for cell cycle and cell fate. Furthermore, data obtained in the last 20 years have shown the involvement of TTCCs in tumor biology, designating them as promising chemotherapeutic targets. However, their activity in the steadily-depolarized membranes of cancer cells, in which most voltage-gated channels are in the inactivated (nonconducting) state, is counter-intuitive. Here we discuss that in cancer cells weak hyperpolarizing stimuli increase the fraction of open TTCCs which, in association with Ca2+-dependent K+ channels, may critically boost membrane hyperpolarization and driving force for Ca2+ entry through different voltage-independent Ca2+ channels. Available evidence also shows that TTCCs participate in positive feedback circuits with signaling effectors, which may warrant a switch-like activation of pro-proliferative and pro-survival pathways in spite of their low availability. Unravelling TTCC modus operandi in the context of non-excitable membranes may facilitate the development of novel anticancer approaches. |
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