Some GPCRs can directly regulate the opening and closing of ion channels to control ion permeability and thus, the cell membrane potential. When the heart rate accelerates, acetylcholine is released. This neurotransmitter binds an associated GPCR in heart muscle cells enabling it to recruit and activate inhibitory G protein. Gαi dissociates from the receptor and the Gβγ subunit. Gβγ binds a potassium channel and opens it. Potassium ions exit the cytosol, making the inside of the membrane more negative or hyperpolarized. A hyperpolarized membrane takes time to return to a less negative or depolarized state. Additionally, Gαi binds adenylyl cyclase to inhibit cyclic AMP production. Lower cAMP concentration closes calcium channels to prevent calcium ions from entering the cell, further delaying membrane depolarization. Delayed membrane depolarization lowers the frequency of heart muscle contraction and slows the heart rate, bringing the body to rest.