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Publication Details
AFRICAN RESEARCH NEXUS
SHINING A SPOTLIGHT ON AFRICAN RESEARCH
medicine
Nadolol block of Nav1.5 does not explain its efficacy in the long QT syndrome
Journal of Cardiovascular Pharmacology, Volume 59, No. 3, Year 2012
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Description
Beta-adrenergic receptor antagonists (β-blockers) are the therapy of choice for the long QT syndrome but their efficacy is not homogeneous: propranolol and nadolol are the most effective, whereas metoprolol is associated with more treatment failures. Propranolol has a blocking effect on the sodium current ("membrane-stabilizing" effect), and it has been hypothesized that the efficacy of nadolol might be due to a similar effect. Accordingly, we used whole-cell patch-clamp recording to assess propranolol, nadolol, and metoprolol block of wild-type or mutant cardiac sodium channels (Nav1.5) coexpressed with β1 subunit in tsA201 cells. Nadolol had a ∼20% non-use-dependent blocking effect on peak sodium current and no effect on the persistent current evoked by the LQT3 mutant A1330D, whereas propranolol blocked Nav1.5 in a use-dependent manner and reduced A1330D persistent current. Metoprolol had no effect on either the peak or persistent current. Analysis of the biophysical properties of the channel revealed that both nadolol and propranolol cause hyperpolarizing shifts on voltage dependence of activation and steady-state inactivation, whereas metoprolol shifts only the activation curve. These results provide partial explanation for the differences between nadolol and metoprolol but do not explain the similar clinical efficacy of nadolol and propranolol. Copyright © 2012 by Lippincott Williams &Wilkins.
Authors & Co-Authors
Besana, Alessandra
Italy, Milan
Irccs Istituto Auxologico Italiano
Wang, Daowen
China, Nanjing
Nanjing Medical University
George, Alfred L.
United States, Nashville
Vanderbilt University
Schwartz, Peter J.
Italy, Pavia
Università Degli Studi Di Pavia
Italy, Pavia
Fondazione Irccs Policlinico San Matteo
South Africa, Cape Town
University of Cape Town
Saudi Arabia, Riyadh
College of Medicine
Statistics
Citations: 28
Authors: 4
Affiliations: 7
Identifiers
Doi:
10.1097/FJC.0b013e31823d2fd1
ISSN:
01602446
e-ISSN:
15334023
Research Areas
Noncommunicable Diseases