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...
Mechanism
Synthesis from 1 study
Leptin turns on a pair of connected channels in appetite-controlling brain cells. The first lets in a little electricity and calcium, which flips on the second channel right next to it. That second channel lets in more calcium exactly where it's needed to fire a signal. If you block calcium right...
Most probable mechanism
When leptin binds to POMC neurons, it opens special channels that let in sodium and a small amount of calcium, which slightly shifts the electrical charge inside the cell. This small shift turns on nearby calcium channels that need a specific voltage to activate. These calcium channels open and let in more calcium right where they are connected to the first channels, which pushes the cell’s charge past the threshold needed to fire signals. If calcium is blocked right at this tight connection point, the signal stops, but if calcium is blocked farther away, the signal still works.
Leptin binds to its receptor on hypothalamic POMC neurons, activating the Jak2-PI3K-PLCγ signaling cascade.
TRPC1/5 channels open in response to signaling, allowing sodium and calcium influx that depolarizes the membrane by approximately 6 mV.
This localized depolarization shifts the membrane voltage into the active window range of adjacent T-type (CaV3.1/CaV3.2) calcium channels, increasing their open probability.
TRPC1/5 and T-type calcium channels form a physical complex that creates a microdomain where calcium influx from TRPC channels directly enhances T-type channel activation.
Calcium entering through T-type channels further depolarizes the membrane to threshold, triggering sodium-dependent action potentials and increasing neuronal excitability.
Fast calcium chelation within the TRPC-T-type microdomain abolishes T-type channel recruitment and action potential firing, while slow chelation outside the microdomain does not.
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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