NALCN sodium leak channels appear to give rise to an inward current that may play an important role in the modulation of bursting and spiking activity. These nonselective cation channels provide a voltage-independent sodium current that also helps slightly depolarize neurons. The channels are regulated by G protein–coupled receptors that can activate or inhibit the NALCN channels depending on the neurotransmitter that binds the receptor and the specific signaling pathway that is involved. Activation of M3 muscarinic receptors by acetylcholine and NK1 by Substance P significantly increases NALCN currents, while activation of CaSR by calcium stops the flow of the currents. Since NALCN sodium leak channels appear to contribute to the depolarization of neurons, their regulation by G-protein coupled receptors may be vital for the alteration of bursting and breathing rhythms.