Model of transmitter and neuropeptide action on CPE cells. Model of transmitter and neuropeptide action on CPE cells. Binding of dopamine (DA) or TPep-NLS to a receptor leads to a reduction in ICl(Ca), carried by Ca2+ dependent Cl- channels (CaCC) and I(Cl-)leak, also carried by CaCC channels. We hypothesize that the blockage of Cl- currents leads to a depolarization of the cell and the activation of voltage-gated Ca2+ channels (CavC) leading to an influx of Ca2+. This initial influx triggers the release of further Ca2+ from ryanodine receptor channel (RyR)-gated endoplasmic reticulum (ER) stores. The sharp rise of [Ca2+]in activates the Ca2+-calmodulin complex, which in turn, upregulates kinases and phosphodiesterases critical for increasing ciliary beating rate. Also present are voltage activated proton channels that play a significant role in pH maintenance and may activate after long depolarizations to aid in the repolarization of the membrane potential. Pluses indicate molecules or actions that increase current amplitude or beating rate, minuses represent inhibitory molecules or actions. Owen M. Woodward, and A. O. Dennis Willows J Exp Biol 2006;209:2765-2773 © The Company of Biologists Limited 2006