In 1914 Dale discovered two types of response to acetylcholine, one mimicked by muscarine and one by nicotine (Dale 1914; Dale and Ewin, 1914). This led to the subsequent discovery of nicotinic and muscarinic acetylcholine receptors. In addition to their pharmacological differences, muscarinic and nicotinic receptors can be differentiated by the mechanism and speed by which their cellular signals are transduced. Nicotinic receptors have a central pore through which sodium and potassium ions pass, resulting in depolarization of the cell membrane. Acetylcholine activates nicotinic receptors by opening the channel, and thus the response is as fast as the channel opening rate (ms). Muscarinic responses are more diverse, both hyperpolarizing and depolarizing cells by a variety of mechanisms. Muscarinic responses are also slower (on the order of 100’s of milliseconds to seconds), due to their interaction with GTP-binding proteins (G-proteins) through which the cellular response is transduced. The slowest signals involve second messengers activated via the G-proteins. Examples include inhibition of adenylyl cyclase (reducing cAMP levels), stimulation of phosphatidylinositol (PI) hydrolysis (raising inositol tris phosphate which stimulates release of calcium from cytosolic stores), and arachidonic acid metabolism. These second messengers, in turn, stimulate a wide variety of responses. For example, mobilized calcium opens calcium-dependent potassium channels, and the activities of protein kinase A and C are dependent on cAMP and PI metabolism, respectively.