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Updated: May 7, 2026
Patch Clamp and Perfusion Techniques for Studying Ion Channels Expressed in Xenopus oocytes
Published on: January 10, 2011
Bio-inspired voltage-dependent calcium channel blockers
Tingting Yang1, Lin-Ling He, Ming Chen
11] Department of Physiology and Cellular Biophysics, Columbia University, College of Physicians and Surgeons, 1150 St Nicholas Avenue, New York, New York 10032, USA [2].
Abstract:
Ca(2+) influx via voltage-dependent CaV1/CaV2 channels couples electrical signals to biological responses in excitable cells. CaV1/CaV2 channel blockers have broad biotechnological and therapeutic applications. Here we report a general method for developing novel genetically encoded calcium channel blockers inspired by Rem, a small G-protein that constitutively inhibits CaV1/CaV2 channels. We show that diverse cytosolic proteins (CaVβ, 14-3-3, calmodulin and CaMKII) that bind pore-forming α1-subunits can be converted into calcium channel blockers with tunable selectivity, kinetics and potency, simply by anchoring them to the plasma membrane. We term this method 'channel inactivation induced by membrane-tethering of an associated protein' (ChIMP). ChIMP is potentially extendable to small-molecule drug discovery, as engineering FK506-binding protein into intracellular sites within CaV1.2-α1C permits heterodimerization-initiated channel inhibition with rapamycin. The results reveal a universal method for developing novel calcium channel blockers that may be extended to develop probes for a broad cohort of unrelated ion channels.
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