Cav3.1 channels control the entry of calcium ions into specific brain cells called POMC neurons, which are involved in signaling fullness after eating.
Mechanism
Synthesis from 3 studies
Cav3.1 calcium channels in satiety brain cells open when the cell membrane becomes more positive or when the amino acid leucine is present. This lets calcium flow in, turning on the cells and signaling fullness. Blocking these channels stops the signal, even if leptin or leucine is present.
Most probable mechanism
A specific calcium channel called Cav3.1 opens in brain cells that signal fullness when the membrane voltage changes or when the amino acid leucine is present. This lets calcium flow into the cells, making them more active and triggering signals that stop eating. The channel works with other channels that first depolarize the cell, and leucine directly makes it easier for Cav3.1 to open. When this channel is blocked or missing, the cells do not activate properly, and the fullness signal does not turn on.
Cav3.1 voltage-gated calcium channels are expressed in hypothalamic pro-opiomelanocortin (POMC) neurons
Leucine binds directly to a hydrophobic pocket on the Cav3.1 channel, lowering its voltage activation threshold and increasing its open probability
Leptin activates TRPC1/5 channels, causing sodium and calcium influx that depolarizes the membrane potential into the active window range of Cav3.1 channels
Depolarization and/or leucine binding causes Cav3.1 channels to open, allowing calcium influx into POMC neurons
Calcium influx through Cav3.1 channels further depolarizes the neuron to threshold, triggering action potentials and increasing intrinsic excitability
Activated POMC neurons initiate downstream signaling pathways that suppress appetite and promote satiety
Evidence from Studies
Supporting (3)
Community contributions welcome
Genetic Deletion of KLHL1 Leads to Hyperexcitability in Hypothalamic POMC Neurons and Lack of Electrical Responses to Leptin
TRPC1/5-CaV3 Complex Mediates Leptin-Induced Excitability in Hypothalamic Neurons
Cav3.1 is a neuronal leucine sensor that mediates satiety and weight loss in response to dietary protein
Contradicting (0)
Community contributions welcome
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