Figure 1. Model of I_CAN activation with hypothesized channel identity and PIP₂ regulation.

Glutamate (triangle) activates group 1 metabotropic glutamate receptors (mGluRs), which then cause G_q-proteins to stimulate phospholipase C (PLC). PLC hydrolyses PIP₂ into diacylgylcerol (DAG) and IP₃, which activates IP₃ receptors (IP₃R) causing Ca²⁺ release from the endoplasmic reticulum (ER). Intracellular Ca²⁺ gates TRPM4 and TRPM5 channels, causing Na⁺ influx and K⁺ efflux that results in depolarization from baseline membrane potentials of –60 mV. PIP₂ also acts directly on TRPM4 and TRPM5 channels to maintain Ca²⁺ sensitivity (dotted arrow).