Ketanserin Inhibits the Transient Outward Current in Rabbit Ventricular Myocytes

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Abstract
The effects of ketanserin on the calcium-independent component of the transient outward potassium current (Ito) was investigated in isolated rabbit ventricular myocytes using the whole-cell patch-clamp technique. Ketanserin concentration-dependently (0.1-100 microM) reduced Ito (IC50 2.25 +/- 2.2 microM; Hill coefficient, nH 0.91), and decreased both the fast and slow Ito inactivation time constants so that the decay of the peak outward current was significantly accelerated. Our results indicate that, in addition to its antagonist activity on 5HT2A/C receptors, ketanserin reduces the calcium-independent component of Ito. Blockade of Ito could explain the proarrhythmic properties of ketanserin in vivo.

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