Advances in cardiac ATP-Sensitive K + channelopathies from molecules to populations

Andre Terzic, Alexey E. Alekseev, Satsuki Yamada, Santiago Reyes, Timothy Mark Olson

Research output: Contribution to journalArticle

9 Citations (Scopus)

Abstract

Deficient cellular energetics set by aberrant K ATP channel function increasingly is implicated in a spectrum of conditions underlying metabolic imbalance and electric instability. 5 Indeed, cardiac K ATP channelopathies are emerging as a recognized disease entity underlying heart failure and arrhythmia. 19 Understanding the molecular structure and function of K ATP channel subunits, 8 and their relationship to cellular metabolic signaling, 99 has been instrumental in interpreting the pathophysiology of channel malfunction associated with heart disease predisposition (Figure 3). 12 From individual patients to populations, variants in K ATP channel genes now have been documented in human dilated cardiomyopathy 21 and atrial fibrillation 20 and as risk factors for electric instability, 93,94 adverse cardiac remodeling, 23 impaired performance under stress, 22 or myocardial infarction. 98 Beyond the initial deciphering of genotype-phenotype relationships, development and application of high-throughput platforms to screen for disrupted coding and regulatory sequences in cardioprotective K ATP channel genes as well as diagnosis of corrupted interactions within the cellular milieu would advance current knowledge regarding this homeostatic channel complex and its implications in cardiovascular medicine. In particular, deconvolution of altered metabolic pathways and signaling cascades associated with pathogenic K ATP channel mutation may offer unique opportunities to pinpoint lesions that stratify the consequences of genetic variation on disease traits. 18 In this regard, it can be anticipated that systems biology and network medicine strategies increasingly will be deployed to resolve the K ATP channel interactome. 11 Mapping of the systems integration of molecules and their respective biological networks in health versus disease will, in turn, guide the judicious development of prognostic discriminators of disease variability and selection of treatment response predictors. 100-102 Advances in the molecular medicine of K ATP channelopathies thus are poised to offer new perspectives in the diagnosis and therapy of individuals and populations. 103-107.

Original languageEnglish (US)
Pages (from-to)577-585
Number of pages9
JournalCirculation: Arrhythmia and Electrophysiology
Volume4
Issue number4
DOIs
StatePublished - Aug 2011

Fingerprint

Channelopathies
Adenosine Triphosphate
Population
Medicine
Molecular Medicine
Systems Integration
Systems Biology
Dilated Cardiomyopathy
Metabolic Networks and Pathways
Molecular Structure
Atrial Fibrillation
Genes
Cardiac Arrhythmias
Heart Diseases
Heart Failure
Myocardial Infarction
Genotype
Phenotype
Mutation

Keywords

  • Genetics
  • Heart diseases
  • Heart failure
  • KATP channels
  • Kir6.2 channel
  • Metabolism
  • Sulfonylurea receptor

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

Cite this

Advances in cardiac ATP-Sensitive K + channelopathies from molecules to populations. / Terzic, Andre; Alekseev, Alexey E.; Yamada, Satsuki; Reyes, Santiago; Olson, Timothy Mark.

In: Circulation: Arrhythmia and Electrophysiology, Vol. 4, No. 4, 08.2011, p. 577-585.

Research output: Contribution to journalArticle

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