PubMed 23255597

Referenced in Channelpedia wiki pages of: none

Automatically associated channels: TRP , TRPM , TRPM4

Title: The sulfonylurea receptor 1 (Sur1)-transient receptor potential melastatin 4 (Trpm4) channel.

Authors: Seung Kyoon Woo, Min Seong Kwon, Alexander Ivanov, Volodymyr Gerzanich, J Marc Simard

Journal, date & volume: J. Biol. Chem., 2013 Feb 1 , 288, 3655-67

PubMed link:

The sulfonylurea receptor 1 (Sur1)-NC(Ca-ATP) channel plays a central role in necrotic cell death in central nervous system (CNS) injury, including ischemic stroke, and traumatic brain and spinal cord injury. Here, we show that Sur1-NC(Ca-ATP) channels are formed by co-assembly of Sur1 and transient receptor potential melastatin 4 (Trpm4). Co-expression of Sur1 and Trpm4 yielded Sur1-Trpm4 heteromers, as shown in experiments with Förster resonance energy transfer (FRET) and co-immunoprecipitation. Co-expression of Sur1 and Trpm4 also yielded functional Sur1-Trpm4 channels with biophysical properties of Trpm4 and pharmacological properties of Sur1. Co-assembly with Sur1 doubled the affinity of Trpm4 for calmodulin and doubled its sensitivity to intracellular calcium. Experiments with FRET and co-immunoprecipitation showed de novo appearance of Sur1-Trpm4 heteromers after spinal cord injury in rats. Our findings depart from the long-held view of an exclusive association between Sur1 and K(ATP) channels and reveal an unexpected molecular partnership with far-ranging implications for CNS injury.