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Pharmacological Dissection of the Crosstalk between Na_V and Ca_V Channels in GH3b6 Cells.

ABSTRACT: Thanks to the crosstalk between Na⁺ and Ca²⁺ channels, Na⁺ and Ca²⁺ homeostasis interplay in so-called excitable cells enables the generation of action potential in response to electrical stimulation. Here, we investigated the impact of persistent activation of voltage-gated Na⁺ (Na_V) channels by neurotoxins, such as veratridine (VTD), on intracellular Ca²⁺ concentration ([Ca²⁺]_i) in a model of excitable cells, the rat pituitary GH3b6 cells, in order to identify the molecular actors involved in Na⁺-Ca²⁺ homeostasis crosstalk. By combining RT-qPCR, immunoblotting, immunocytochemistry, and patch-clamp techniques, we showed that GH3b6 cells predominantly express the Na_V1.3 channel subtype, which likely endorses their voltage-activated Na⁺ currents. Notably, these Na⁺ currents were blocked by ICA-121431 and activated by the β-scorpion toxin Tf2, two selective Na_V1.3 channel ligands. Using Fura-2, we showed that VTD induced a [Ca²⁺]_i increase. This effect was suppressed by the selective Na_V channel blocker tetrodotoxin, as well by the selective L-type Ca_V channel (LTCC) blocker nifedipine. We also evidenced that crobenetine, a Na_V channel blocker, abolished VTD-induced [Ca²⁺]_i elevation, while it had no effects on LTCC. Altogether, our findings highlight a crosstalk between Na_V and LTCC in GH3b6 cells, providing a new insight into the mode of action of neurotoxins.

SUBMITTER: Rethore L

PROVIDER: S-EPMC8775721 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Pharmacological Dissection of the Crosstalk between Na_V and Ca_V Channels in GH3b6 Cells.

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Dataset Information

Pharmacological Dissection of the Crosstalk between NaV and CaV Channels in GH3b6 Cells.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets

Pharmacological Dissection of the Crosstalk between Na_V and Ca_V Channels in GH3b6 Cells.