Referenced in: none

Automatically associated channels: Kv1.4 , Kv1.5 , Kv11.1 , Kv3.1 , Kv4.3 , Slo1

Title: Effects of lobeline, a nicotinic receptor ligand, on the cloned Kv1.5.

Authors: Imju Jeong, Bok Hee Choi, Sang June Hahn

Journal, date & volume: Pflugers Arch., 2010 Oct , 460, 851-62

PubMed link: http://www.ncbi.nlm.nih.gov/pubmed/20734202

Abstract
The goal of the present study was to examine the effects of lobeline, an agonist at nicotinic receptors, on cloned Kv channels, Kv1.5, Kv3.1, Kv4.3, and human ether-a-gogo-related gene (HERG), which are stably expressed in Chinese hamster ovary (CHO) or human embryonic kidney 293 (HEK293) cells. Whole-cell patch-clamp experiments revealed that lobeline accelerated the decay rate of Kv1.5 inactivation, decreasing the current amplitude at the end of the pulse in a concentration-dependent manner with a half-maximal inhibitory concentration (IC(50)) value of 15.1 μM. Using a time constant for the time course of drug-channel interaction, the apparent association (k(+1)), and dissociation rate (k(-1)) constants were 2.4 μΜ(-1) s(-1) and 40.9 s(-1), respectively. The calculated K(D) was 17.0 μΜ. Lobeline slowed the decay rate of the tail current, resulting in a tail crossover phenomenon. The inhibition of Kv1.5 by lobeline steeply increased at potentials between -10 and +10 mV, which corresponds to the voltage range of channel activation. At more depolarized potentials a weaker voltage dependence was observed (δ=0.26). The voltage dependence of the steady-state activation curve was not affected by lobeline, but lobeline shifted the steady-state inactivation curve of Kv1.5 in the hyperpolarizing direction. Lobeline produced use-dependent inhibition of Kv1.5 at frequencies of 1 and 2 Hz, and slowed the recovery from inactivation. Lobeline also inhibited Kv3.1, Kv4.3, and HERG in a concentration-dependent manner, with IC(50) values of 21.7, 28.2, and 0.34 μM, respectively. These results indicate that lobeline produces a concentration-, time-, voltage-, and use-dependent inhibition of Kv1.5, which can be interpreted as an open-channel block mechanism.