Propranolol inhibits the human ether-a-go-go-related gene potassium channels.

Propranolol is a noncardioselective beta-adrenergic antagonist that has been recently reported to prolong the QTc interval on the surface electrocardiogram in humans when overdosed [Farhangi, V., Sansone, R.A. (2003). QTc prolongation due to propranolol overdose. Int. J. Psychiatry Med. 33, 201-202.]. To examine the underlying mechanisms for these clinical findings, we studied the effects of propranolol on the human cardiac potassium channels encoded by the ether-a-go-go-related gene (ERG) using the whole cell voltage-clamp technique. We found that propranolol blocked hERG currents in a concentration-dependent manner with an IC50 of 9.9+/-1.3 microM which is relevant to the predicted plasma level of propranolol in this case report. The present study demonstrated that propranolol can inhibit hERG channels. The interaction between propranolol and hERG channels could lead to delayed cardiac repolarization and might be a molecular mechanism for the previously reported QTc prolongation when propranolol is overdosed.

[1]  P. C. Viswanathan,et al.  Novel characteristics of a misprocessed mutant HERG channel linked to hereditary long QT syndrome. , 2000, American journal of physiology. Heart and circulatory physiology.

[2]  M. Sanguinetti,et al.  A mechanistic link between an inherited and an acquird cardiac arrthytmia: HERG encodes the IKr potassium channel , 1995, Cell.

[3]  D M Roden,et al.  The long QT syndromes: genetic basis and clinical implications. , 2000, Journal of the American College of Cardiology.

[4]  A. Camm,et al.  Effect of intravenous propranolol on QT interval. A new method of assessment. , 1980, British heart journal.

[5]  M. Leider.  Goodman & Gilman's The Pharmacological Basis of Therapeutics , 1985 .

[6]  Hans Larsson,et al.  Pharmacokinetics of propranolol , 1981, Journal of Pharmacokinetics and Biopharmaceutics.

[7]  B. Sakmann,et al.  Improved patch-clamp techniques for high-resolution current recording from cells and cell-free membrane patches , 1981, Pflügers Archiv.

[8]  A. Camm,et al.  Relationships between preclinical cardiac electrophysiology, clinical QT interval prolongation and torsade de pointes for a broad range of drugs: evidence for a provisional safety margin in drug development. , 2003, Cardiovascular research.

[9]  S. Viskin.  Long QT syndromes and torsade de pointes , 1999, The Lancet.

[10]  W. Stigelman,et al.  Goodman and Gilman's the Pharmacological Basis of Therapeutics , 1986 .

[11]  I. Francetic,et al.  Dose-dependent bioavailability of propranolol. , 1986, International journal of clinical pharmacology, therapy, and toxicology.

[12]  R. Sansone,et al.  QTc Prolongation Due to Propranolol Overdose , 2003, International journal of psychiatry in medicine.