New evidence reveals that the common electrolyte disorder hypokalemia can induce K2P1 channels that are normally selective for K+ to break the rules and conduct Na+. This defiant behavior leads to paradoxical depolarization of many cells in the heart, increasing the risk for lethal arrhythmia. The new research resolves a mystery uncovered 50 years ago and bestows an array of new riddles. Here, I discuss how K2P1 might achieve this alchemy--through stable residence of the K+ selectivity filter in a Na+-conductive state between its open and C-inactive configurations--and predict that other K+ channels and environmental stimuli will be discovered to produce the same excitatory misconduct.
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http://dx.doi.org/10.1126/scisignal.2002225 | DOI Listing |
Front Cell Neurosci
November 2024
Department of Functional Neuroanatomy, Institute of Anatomy and Cell Biology, Heidelberg University, Heidelberg, Germany.
Processing of auditory signals critically depends on the neuron's ability to fire brief, precisely timed action potentials (APs) at high frequencies and high fidelity for prolonged times. This requires the expression of specialized sets of ion channels to quickly repolarize neurons, prevent aberrant AP firing and tightly regulate neuronal excitability. Although critically important, the regulation of neuronal excitability has received little attention in the auditory system.
View Article and Find Full Text PDFFront Physiol
October 2024
Department of Anesthesiology, The Affiliated Hospital of Zunyi Medical University, Zunyi, Guizhou, China.
Proc Natl Acad Sci U S A
October 2024
University Claude Bernard Lyon 1, MeLiS, CNRS UMR 5284, INSERM U1314, Lyon 69008, France.
Nat Commun
October 2024
Department of Electronic and Computer Engineering, The Hong Kong University of Science and Technology, Hong Kong, P. R. China.
Microglia, the primary immune cells in the central nervous system, play a critical role in regulating neuronal function and fate through their interaction with neurons. Despite extensive research, the specific functions and mechanisms of microglia-neuron interactions remain incompletely understood. In this study, we demonstrate that microglia establish direct contact with myelinated axons at Nodes of Ranvier in the spinal cord of mice.
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