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Unique properties of the ATP-sensitive K⁺ channel in the mouse ventricular cardiac conduction system.

Abstract
Background- The specialized cardiac conduction system (CCS) expresses a unique complement of ion channels that confer a specific electrophysiological profile. ATP-sensitive potassium (K(ATP)) channels in these myocytes have not been systemically investigated. Methods and Results- We recorded K(ATP) channels in isolated CCS myocytes using Cntn2-EGFP reporter mice. The CCS K(ATP) channels were less sensitive to inhibitory cytosolic ATP compared with ventricular channels and more strongly activated by MgADP. They also had a smaller slope conductance. The 2 types of channels had similar intraburst open and closed times, but the CCS K(ATP) channel had a prolonged interburst closed time. CCS K(ATP) channels were strongly activated by diazoxide and less by levcromakalim, whereas the ventricular K(ATP) channel had a reverse pharmacological profile. CCS myocytes express elevated levels of Kir6.1 but reduced Kir6.2 and SUR2A mRNA compared with ventricular myocytes (SUR1 expression was negligible). SUR2B mRNA expression was higher in CCS myocytes relative to SUR2A. Canine Purkinje fibers expressed higher levels of Kir6.1 and SUR2B protein relative to the ventricle. Numeric simulation predicts a high sensitivity of the Purkinje action potential to changes in ATP:ADP ratio. Cardiac conduction time was prolonged by low-flow ischemia in isolated, perfused mouse hearts, which was prevented by glibenclamide. Conclusions- These data imply a differential electrophysiological response (and possible contribution to arrhythmias) of the ventricular CCS to K(ATP) channel opening during periods of ischemia.
AuthorsLi Bao, Eirini Kefaloyianni, Joshua Lader, Miyoun Hong, Gregory Morley, Glenn I Fishman, Eric A Sobie, William A Coetzee
JournalCirculation. Arrhythmia and electrophysiology (Circ Arrhythm Electrophysiol) Vol. 4 Issue 6 Pg. 926-35 (Dec 2011) ISSN: 1941-3084 [Electronic] United States
PMID21984445 (Publication Type: Journal Article, Research Support, N.I.H., Extramural)
Chemical References
  • Abcc8 protein, mouse
  • Abcc8 protein, rat
  • Abcc9 protein, mouse
  • Anti-Arrhythmia Agents
  • Contactin 2
  • KATP Channels
  • Kir6.2 channel
  • Potassium Channel Blockers
  • Potassium Channels, Inwardly Rectifying
  • RNA, Messenger
  • Receptors, Drug
  • Sulfonylurea Receptors
  • enhanced green fluorescent protein
  • uK-ATP-1 potassium channel
  • Green Fluorescent Proteins
  • Adenosine Triphosphate
Topics
  • ATP-Binding Cassette Transporters (metabolism)
  • Action Potentials
  • Adenosine Triphosphate (metabolism)
  • Animals
  • Anti-Arrhythmia Agents (pharmacology)
  • Arrhythmias, Cardiac (metabolism, physiopathology, prevention & control)
  • Computer Simulation
  • Contactin 2 (genetics)
  • Disease Models, Animal
  • Green Fluorescent Proteins (genetics, metabolism)
  • Heart Ventricles (drug effects, metabolism, physiopathology)
  • KATP Channels (drug effects, genetics, metabolism)
  • Kinetics
  • Mice
  • Mice, Transgenic
  • Models, Cardiovascular
  • Myocardial Ischemia (metabolism, physiopathology)
  • Myocytes, Cardiac (drug effects, metabolism)
  • Numerical Analysis, Computer-Assisted
  • Patch-Clamp Techniques
  • Perfusion
  • Potassium Channel Blockers (pharmacology)
  • Potassium Channels, Inwardly Rectifying (metabolism)
  • Purkinje Fibers (drug effects, metabolism, physiopathology)
  • RNA, Messenger (metabolism)
  • Rats
  • Rats, Sprague-Dawley
  • Receptors, Drug (metabolism)
  • Sulfonylurea Receptors

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