AuPS Logo
Previous Next PDF

Effects of lobeline, a nicotinic receptor ligand, on the cloned cardiac K+ channels, Kv1.5, Kv3.1 and Kv4.3

I.J. Jeong,1 S.J. Hahn1 and B.H. Choi,2 1Department of Physiology, Medical Research Center, College of Medicine, The Catholic University of Korea, Seoul 137701, Republic of Korea and 2Department of Pharmacology, Chonbuk National University, Jeonju, Republic of Korea.

The effects of lobeline, an agonist at nicotinic receptors, on Kv1.5, Kv3.1 and Kv4.3 stably expressed in CHO cells were examined using the whole-cell patch-clamp methods. 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 (IC50) 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 ± 0.2 μΜ−1s−1 and 40.9 ± 11.5 s−1, respectively. The calculated KD value derived by k−1/k+1 was 17.0 μΜ. Lobeline slowed the rate of decay of the tail current, resulting in a tail crossover phenomenon. The inhibition of Kv1.5 by lobeline steeply decreased at potentials between −20 and +10 mV, which corresponds to the voltage range of channel activation. At more depolarized potential, a weaker voltage-dependence was observed with a value of electrical distance (δ) of 0.26. The voltage dependence of steady-state activation curve was not affected by lobeline, but lobeline shifted the steady-state inactivation curves of Kv1.5 in the hyperpolarizing direction. Lobeline produced use-dependent inhibition of Kv1.5 at a frequency of 1 Hz and 2 Hz and slowed the recovery from inactivation. Lobeline also inhibited Kv3.1 and Kv4.3 in a concentration-dependent manner with an IC50 value of 21.7 μM and 28.2 μM, respectively. These results indicate that lobeline blocks Kv1.5 by binding to the open state of the channels.