In mouse brain cells called POMC neurons, the hormone leptin triggers a sequence of ion channel activations that increases calcium influx and makes the cells fire electrical signals more readily.

In mouse brain cells called POMC neurons, leptin does not directly change how T-type calcium channels open or close; instead, it affects these channels indirectly by causing the cell membrane to depolarize through activation of TRPC channels.

In mouse brain cells called POMC neurons, blocking TRPC or T-type calcium channels stops leptin from making the cells more active, including preventing the decrease in the minimum current needed to trigger firing and the increase in firing rate.

When CaV3.1 T-type calcium channels are overexpressed in specific hypothalamic neurons, these neurons become more active at rest and fail to respond to leptin, even though the leptin receptors and signaling pathways function normally.

In mouse brain cells called POMC neurons, removing calcium ions with BAPTA blocks the increase in electrical activity caused by leptin, but removing calcium with EGTA does not. This shows that calcium entering near a specific protein complex is necessary for the sustained electrical response to leptin, but not for the initial electrical change.

In mice lacking the KLHL1 gene, blocking T-type calcium channels with a specific drug restores the ability of leptin to activate brain cells that control appetite, showing that excessive electrical activity in these cells—not a broken leptin receptor—causes leptin resistance.