PBIO SEMINAR SERIES

Calmodulin regulation of voltage-gated calcium channels—Smart Ca²⁺ detection and biological impact

December 01, 2005
Lamport Lecture
3:30-4:30
CHDD 150

David Yue
Professor of Biomedical Engineering Johns Hopkins University
Speaker's website

Host: Stan Froehner

Ca²⁺ channels are richly modulated by calmodulin (CaM), rendering these ion channels as integrative crossroads for Ca²⁺ signaling. Fitting with the biological importance of such crossroads, CaM exhibits unusually powerful regulatory capabilities in the setting of Ca²⁺ channels. Even before the elevation of Ca²⁺, apoCaM (Ca²⁺-free) already preassociates with the C-termini of CaV1-2 channels, casting CaM as a resident Ca²⁺ sensor. Ca²⁺ binding to the N- or C-terminal lobes of CaM selectively triggers distinct forms of feedback regulation of channel opening, enabling CaM to ‘bifurcate’ the local Ca²⁺ signal into two outputs. Moreover, the lobes of CaM appear to decode different streams of information from within the same channel nanodomain, with the N- and C-terminal lobes of CaM respectively specialized to respond to local versus global Ca²⁺ activity. The impact of such ion channel regulation on cardiac- and neuro-biology will be explored.