An arrhythmia susceptibility gene in Caenorhabditis elegans

Ki Ho Park, Federico Sesti

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

kcne are evolutionarily conserved genes that encode accessory subunits of voltage-gated K+ (Kv) channels. Missense mutations in kcne1, kcne2, and kcne3 are linked to congenital and acquired channelopathies in Homo sapiens. Here we show an unique example of conservation of kcne activities at genetic, physiological, functional, and pathophysiological level in Caenorhabditis elegans. Thus, mps-4 is the homologue of kcne1 that operates in human heart and inner ear. Like its KCNE relatives, MPS-4 assembles with a Kv channel, EXP-2, to form a complex that controls pharyngeal muscle contractility. MPS-4 modulates EXP-2 function in a similar fashion as KCNE proteins endow human channels. When defective, MPS-4, can induce abnormal repolarization by mechanisms that resemble the way KCNE proteins are thought to provoke arrhythmia in human heart. Mutation of a conserved aspartate residue associated with human disease (MPS-4-D74N) alters the functional attributes of the C. elegans current. Taken together these data underscore a significant conservation of KCNE activities in different pumps. This implies that C. elegans can develop into a system to study the molecular and genetic basis of KCNE-mediated muscle contractility and disease states.

Original languageEnglish (US)
Pages (from-to)19799-19807
Number of pages9
JournalJournal of Biological Chemistry
Volume282
Issue number27
DOIs
StatePublished - Jul 6 2007

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology

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