Department of Drug Design and Pharmacology, KU
Title: Molecular basis for calcium regulation of the background sodium conductance in neurons
Abstract: Numerous types of neurons display a constitutive background sodium current, which regulates the resting membrane potential and spontaneous firing. This leak current is crucial for a number of neurological functions, incl breathing and location and had been proposed to mediated by the non-selective sodium leak channel NALCN. Indeed, NALCN knockout in mice is neonathal lethal and humans carrying NALCN mutations display severe neurological and developmental phenotypes. However, the molecular function of NALCN remained elusive. Here, we present the identification of proteins that assemble to form the functional NALCN channelosome, a protein complex that displays voltage-dependent gating and is inhibited by extracellular calcium. We propose that this protein complex forms the molecular basis for calcium regulation of the background sodium conductance in neurons.