A fundamental question in cell biology is how different receptor-mediated signaling cascades, despite utilizing many of the same intracellular components, can generate specific cellular responses. Delmas and colleagues (in this issue of Neuron) address this question in relation to the muscarinic acetylcholine receptor (M(1)AchR) and the B(2) bradykinin receptor (B(2)R). Using Trp channel isoforms as biosensors for PLC stimulation in response to agonist activation, they demonstrate a role for signaling microdomains in the induction of such selective responses.