PIP2 sterically inhibits pore opening of a CNG channel

Cyclic nucleotide-gated (CNG), and hyperpolarization-activated and cyclic nucleotide-modulated (HCN) channels are key players in signaling cascades related to vision and olfaction, as well as pacemaking and neuropathic pain, respectively. Despite their structural homology, their functional regulation is quite different. For instance, the signaling lipid PIP2 inhibits CNG channels, but activates HCN channels. In both cases, the underlying mechanism is unknown.