title: Delayed pharyngeal repolarization promotes abnormal calcium buildup in aging muscle.
abstract: In the pharynx of Caenorhabditis elegans, the accessory subunit MPS-4, homolog to human KCNE1, forms a complex with K(+) channel EXP-2 that terminates the action potential. An aspartate residue critical for KCNE1 function, asp76, is conserved in MPS-4 (asp74). Here, we studied the effects of D74N-MPS-4 on the aging pharynx. Electrophysiological studies showed that D74N delays pharyngeal repolarization. Pharynxes of transgenic worms expressing D74N exhibited higher levels of intracellular calcium compared to normal pharynxes. Accordingly, loss of pharyngeal function was accelerated in aging D74N worms. The pharyngeal action potential resembles the action potential that controls the mechanical activity of human left ventricle. Hence, these findings argue that the hearts of patients affected by delayed repolarization, a condition known as long QT syndrome, may experience dysregulated calcium homeostasis.
authors.affiliation: University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Department of Neuroscience and Cell Biology, Piscataway, NJ 08854, USA.
authors.forename: Przemyslaw
authors.initials: P
authors.lastname: Swiatkowski
authors.forename: Federico
authors.initials: F
authors.lastname: Sesti
mesh_terms: D000200:Action Potentials / Q000502:physiology*; D000375:Aging / Q000378:metabolism*; D000818:Animals; D001224:Aspartic Acid / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D017173:Caenorhabditis elegans / Q000502:physiology*; D029742:Caenorhabditis elegans Proteins / Q000235:genetics / Q000378:metabolism; D002118:Calcium / Q000378:metabolism*; D006352:Heart Ventricles / Q000378:metabolism / Q000473:pathology; D006801:Humans; D008133:Long QT Syndrome / Q000378:metabolism / Q000473:pathology; D008954:Models, Biological; D009154:Mutation; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D010614:Pharynx / Q000378:metabolism*; D015221:Potassium Channels / Q000235:genetics / Q000378:metabolism; D024642:Potassium Channels, Voltage-Gated / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011485:Protein Binding; D020033:Protein Isoforms / Q000737:chemistry / Q000235:genetics / Q000378:metabolism; D021122:Protein Subunits / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D017386:Sequence Homology, Amino Acid
chemical_list: D029742:Caenorhabditis elegans Proteins; C489622:KCNE1 protein, human; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D020033:Protein Isoforms; D021122:Protein Subunits; C403529:exp-2 protein, C elegans; D001224:Aspartic Acid; D002118:Calcium