Functional Stoichiometry and Local Enrichment of Calmodulin Interacting with Ca²⁺ Channels

Calmodulin (CaM) interactions with Ca²⁺ channels mediate both Ca²⁺ regulation of channels and local Ca²⁺ triggering of transcription factors implicated in neuronal memory. Crucial to these functions are the number of CaM molecules (CaMs) regulating each channel, and the number of CaMs privy to the local Ca²⁺ signal from each channel. To resolve these parameters, we fused L-type Ca²⁺ channels to single CaM molecules. These chimeric molecules revealed that a single CaM directs L-type channel regulation. Similar fusion molecules were used to estimate the local CaM concentration near Ca²⁺ channels. This estimate indicates marked enrichment of local CaM, as if a "school" of nearby CaMs were poised to enhance the transduction of local Ca²⁺ entry into diverse signaling pathways.