Pergolide block of the cloned Kv1.5 potassium channels.

Imju Jeong, Bok Hee Choi, Sang June Hahn

Naunyn-Schmiedeberg's archives of pharmacology 2013 Feb

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Pergolide mesylate, an ergot-derivative dopamine receptor agonist, is prescribed for the management of patients with Parkinson's disease. Pergolide caused vasoconstriction in a pulmonary artery. Kv1.5 channel is highly expressed in pulmonary arterial smooth muscle cells, where it plays an important role as a determinant of vascular tone. In the present study, we investigated the effects of pergolide on Kv1.5 stably expressed in Chinese hamster ovary cells using the whole-cell patch-clamp technique. The Kv1.5 block by pergolide was concentration-, time-, voltage-, and use-dependent. Pergolide blocked Kv1.5 currents in a concentration-dependent manner, with an IC(50) value of 15.4 μM and a Hill coefficient of 1.7. The activation and inactivation of Kv1.5 were significantly accelerated by pergolide in a concentration-dependent manner. The apparent association and dissociation rate constants were 0.43 μM(-1) s(-1) and 8.34 s(-1), respectively, with a K (D) value of 19.1 μM. Pergolide slowed deactivation kinetics of Kv1.5, resulting in a tail crossover phenomenon. The block of Kv1.5 by pergolide was voltage-dependent, increasing significantly at test potentials from -10 to +10 mV, whereas the current was reduced slightly with a shallower voltage dependence in the range between +20 and +50 mV (δ = 0.34). There was a significant hyperpolarizing shift in the voltage dependence of steady-state inactivation of Kv1.5. Pergolide produced a use-dependent Kv1.5 block at 1 and 2 Hz, and also slowed the time course for recovery from inactivation. These results suggest that pergolide has an affinity for the open and inactivated states of Kv1.5 channels.

Citation

Imju Jeong, Bok Hee Choi, Sang June Hahn. Pergolide block of the cloned Kv1.5 potassium channels. Naunyn-Schmiedeberg's archives of pharmacology. 2013 Feb;386(2):125-33