TY - JOUR
T1 - Differences in action potential and early afterdepolarization properties in LQT2 and LQT3 models of long QT syndrome
AU - Studenik, Christian R.
AU - Zhou, Zhengfeng
AU - January, Craig T.
PY - 2001
Y1 - 2001
N2 - 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 (IKr) with the drug E-4031, and LQT3 was simulated by slowing of the sodium current (INa) 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.
AB - 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 (IKr) with the drug E-4031, and LQT3 was simulated by slowing of the sodium current (INa) 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.
KW - ATX II
KW - E-4031
KW - Early afterdepolarizations
KW - Fast Fourier transforms
KW - Long QT syndrome
KW - Rabbit ventricular myocytes
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U2 - 10.1038/sj.bjp.0703770
DO - 10.1038/sj.bjp.0703770
M3 - Article
C2 - 11156564
AN - SCOPUS:0035143074
SN - 0007-1188
VL - 132
SP - 85
EP - 92
JO - British Journal of Pharmacology
JF - British Journal of Pharmacology
IS - 1
ER -