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EMERGING TECHNOLOGY

Engineering Proteins for Custom Inhibition of Ca_V Channels

Xianghua Xu and Henry M. Colecraft

Department of Physiology and Cellular Biophysics, College of Physicians and Surgeons, Columbia University, New York, New York, hc2405{at}columbia.edu

The influx of Ca²⁺ ions through voltage-dependent calcium (Ca_V) channels links electrical signals to physiological responses in all excitable cells. Not surprisingly, blocking Ca_V channel activity is a powerful method to regulate the function of excitable cells, and this is exploited for both physiological and therapeutic benefit. Nevertheless, the full potential for Ca_V channel inhibition is not being realized by currently available small-molecule blockers or second-messenger modulators due to limitations in targeting them either to defined groups of cells in an organism or to distinct subcellular regions within a single cell. Here, we review early efforts to engineer protein molecule blockers of Ca_V channels to fill this crucial niche. This technology would greatly expand the toolbox available to physiologists studying the biology of excitable cells at the cellular and systems level.