Differences in action potential and early afterdepolarization properties in LQT2 and LQT3 models of long QT syndrome.
1. Long OT syndrome has many causes from both acquired and congenital disorders. For the congenital disorders, their presentation and disease course are not identical. We studied two pharmacological models of long QT syndrome (LQT) to identify differences in cellular electrophysiological properties that may account for this. LQT2 was simulated by suppression of the rapidly activating delayed rectifier potassium current (I(Kr)) with the drug E-4031, and LQT3 was simulated by slowing of the sodium current (I(Na)) decay with the toxin ATX II. 2. Single rabbit ventricular cell action potentials were studied using the amphotericin B perforated patch clamp technique. Action potential and early afterdepolarization (EAD) properties were rigorously defined by the frequency power spectra obtained with fast Fourier transforms. 3. The E-4031 (n=43 myocytes) and ATX II (n=50 myocytes) models produced different effects on action potential and EAD properties. The major differences are that ATX II, compared with E-4031, caused greater action potential prolongation, more positive plateau voltages, lower amplitude EADs with less negative take-off potentials, greater time to the EAD peak voltage, and longer duration EADs. Despite causing greater action potential prolongation, the incidence of EAD induction was much less with the ATX II model (28%) than with the E-4031 model (84%). Thus these two pharmacological models have strikingly different cellular electrophysiological properties. 4. Our findings provide cellular mechanisms that may account for some differences in the clinical presentation of LQT2 and LQT3.
Studenik
C R
CR
Institute of Pharmacology and Toxicology, University of Vienna, Vienna, Austria. Christian.Studenik@univie.ac.at
Zhou
Z
Z
January
C T
CT
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D002469:Cell Separation; D004558:Electric Stimulation; D004594:Electrophysiology; D005583:Fourier Analysis; D006321:Heart / Q000503:physiopathology; D066298:In Vitro Techniques; D008133:Long QT Syndrome / Q000139:chemically induced / Q000503:physiopathology*; D018408:Patch-Clamp Techniques; D010880:Piperidines / Q000494:pharmacology; D026902:Potassium Channel Blockers; D011725:Pyridines / Q000494:pharmacology; D011817:Rabbits; D013779:Tetrodotoxin / Q000633:toxicity
D000889:Anti-Arrhythmia Agents; D010880:Piperidines; D026902:Potassium Channel Blockers; D011725:Pyridines; C063968:E 4031; D013779:Tetrodotoxin