In mouse hypothalamic neurons, TRPC1 and TRPC5 ion channels bind directly to CaV3.1 and CaV3.2 T-type calcium channels to form a stable protein complex.
Mechanism
Synthesis from 1 study
In hunger-controlling brain cells, specific protein channels stick together to form a team. When leptin signals that the body is full, the first channels let in sodium and calcium, which slightly warms up the cell’s electrical charge. This small change turns on the nearby calcium channels, which...
Most probable mechanism
Leptin triggers a chain reaction in hunger-controlling brain cells where specific protein channels stick together and work as a team: first, they let in sodium and calcium, which slightly warms up the cell's electrical charge; this small change turns on nearby calcium channels that need a little push to activate; those channels then flood the cell with more calcium, which fires off electrical signals that tell the brain it's full.
Leptin binds to its receptor on hypothalamic POMC neurons, initiating intracellular signaling through Jak2-PI3K-PLCγ.
TRPC1 and TRPC5 channels open in response to PLCγ activation, allowing sodium and calcium ions to enter the neuron.
Ion influx through TRPC1/5 channels depolarizes the membrane potential by approximately 6 mV, shifting it into the activation range of adjacent T-type calcium channels.
CaV3.1 and CaV3.2 T-type calcium channels, physically coupled to TRPC1/5 in a macromolecular complex, increase their open probability due to the localized depolarization.
Calcium influx through CaV3.1/3.2 channels further depolarizes the membrane to threshold, triggering voltage-gated sodium channels to generate action potentials.
Calcium entry through the TRPC1/5-CaV3 complex occurs within a microdomain where local calcium concentration is sufficient to sustain excitability, protected from global calcium buffering.
TRPC1, TRPC5, CaV3.1, and CaV3.2 proteins form a stable macromolecular complex that enables direct functional coupling between sodium/calcium influx and T-type channel activation.
Evidence from Studies
Supporting (1)
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TRPC1/5-CaV3 Complex Mediates Leptin-Induced Excitability in Hypothalamic Neurons
Contradicting (0)
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