What are the mechanisms by which acetylcholine affects heart rate?

Answer 1

Wowsers, a highly technical question. This will be a highly technical answer. Acetylcholine (ACh) is a neurotransmitter which biochemically binds to AChR receptors on striated muscle fibers including the heart muscle. There are two types of these receptors, the nicotinic acetylcholine receptors (nAChR) and muscarinic acetylcholine receptors (mAChR), both of which are stimulated by ACh. When an ACh molecule binds to an M2 level mAChR in the heart muscle, it catalyzes the conversion of guanosine diphosphate (GDP) to guanosine triphosphate (GTP). This triggers activation of a transducing G protein that binds to and opens a potassium K+ channel, which hyperpolarizes the heart muscle plasma membrane. This causes the rate and force of the heart contractions to decrease. Activation of this process ends when the GTP is hydrolized back to GDP. Note that in this process, stimulation of the neuroreceptor causes a decrease in function, the opposite of what we might expect. ACh does affect other receptors throughout the body as we might expect by increasing the rate of functions in the brain, muscles, glands and throughout the nervous system. The activity of ACh is kept in check by the enzyme acetylcholinesterase, which breaks down ACh into inactive components. Many "nerve gas" agents (such as Sarin) work by inhibiting ACh-ase; this allows ACh to run rampant through the body, overstimulating the brain and nervous system while depressing the functions of the heart. Many of our modern insecticides are ACh-ase inhibitors, which is why insects flutter around uncontrollably until they die.