Research Paper
Subject Category: Cardiovascular and pulmonary pharmacology
British Journal of Pharmacology (2008) 153, 448–458; doi:10.1038/sj.bjp.0707579; published online 26 November 2007
Chlorthalidone inhibits the KvLQT1 potassium current in guinea-pig ventricular myocytes and oocytes from Xenopus laevis
C Mancilla-Simbro1, A López1, E Martinez-Morales1, E Soto-Perez-de-Celis1, L Millan-PerezPeña1, R Tsushima2 and E M Salinas-Stefanon1
- 1Instituto de Fisiología, B. Universidad Autónoma de Puebla, Ciudad Universitaria, Puebla, Puebla, México
- 2Instituto de Fisiología, B. Universidad Autónoma de Puebla and School of Medicine, University of Toronto, Toronto, Ontario, Canada
Correspondence: Professor EM Salinas-Stefanon, Instituto de Fisiología, B. Universidad Autónoma de Puebla, Av 14 Sur no. 6301, Ciudad Universitaria San Manuel, Puebla 72501, México. E-mail: esalinas@siu.buap.mx
Received 17 August 2007; Revised 26 September 2007; Accepted 10 October 2007; Published online 26 November 2007.
Abstract
Background and purpose:
Chlorthalidone is used for the treatment of hypertension as it produces a lengthening of the cardiac action potential. However, there is no experimental evidence that chlorthalidone has electrophysiological effects on the potassium currents involved in cardiac repolarization.
Experimental approach:
Ventricular myocytes and oocytes, transfected with human ionic channels that produce IK current, were exposed to different concentrations of chlorthalidone. Action potentials and potassium currents were recorded using a patch clamp technique. To determine which component of the current was affected by chlorthalidone, human channel proteins (hERG, minK and KvLQT1) were used.
Key results:
Chlorthalidone prolonged the ventricular action potential at 50 and 90% by 13 and 14%, respectively. The cardiac potassium currents I
to and IK1 were not affected by chlorthalidone at any concentration, whereas the delayed rectifier potassium current, IK, was blocked in a dose-response, voltage-independent fashion. In our preparation, 100 
M chlorthalidone blocked the two components of the delayed rectifier potassium current with the same potency (50.1
5% for IKr and 54.66% for IKs) (n=7, P<0.05). The chlorthalidone-sensitive current was slow and saturated at potentials greater than +30 mV. In our conditions only the KvLQT1 potassium current was affected by the drug, by 14%.
Conclusions and implications:
Chlorthalidone was demonstrated to have a direct effect on cardiac ventricular myocytes; it blocked the delayed rectifier potassium current (IK), specifically the KvLQT1 component of the potassium current. These results indicate that it has potential for use as an antiarrhythmic but further studies are needed.
Keywords:
chlorthalidone, thiazide diuretics, cardiac potassium currents, IK, patch clamp, isolated cardiac myocytes, KvLQT1 current, oocytes
Abbreviations:
Ito, transient outward potassium current; IK, delayed rectifier potassium current; IKr, fast component of IK; IKs, slow component of IK; IK1, inward rectifier potassium current; hERG, human ether a go-go channel; minK, minimum potassium channel; KvLQT1, potassium long Q-T channel
