Back to Search
Start Over
Effects of lobeline, a nicotinic receptor ligand, on the cloned Kv1.5.
- Source :
-
Pflügers Archiv: European Journal of Physiology . Oct2010, Vol. 460 Issue 5, p851-862. 12p. 8 Graphs. - Publication Year :
- 2010
-
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) value of 15.1 μM. Using a time constant for the time course of drug-channel interaction, the apparent association ( k), and dissociation rate ( k) constants were 2.4 μΜ s and 40.9 s, respectively. The calculated K 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 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. [ABSTRACT FROM AUTHOR]
- Subjects :
- *LIGANDS (Biochemistry)
*NICOTINE
*CLONING
*GENETIC engineering
*HAMSTERS
Subjects
Details
- Language :
- English
- ISSN :
- 00316768
- Volume :
- 460
- Issue :
- 5
- Database :
- Academic Search Index
- Journal :
- Pflügers Archiv: European Journal of Physiology
- Publication Type :
- Academic Journal
- Accession number :
- 53505731
- Full Text :
- https://doi.org/10.1007/s00424-010-0868-3