Effects of some potassium channel blockers on the ionic currents in myelinated nerve.
The effects of some potassium channel blockers on the ionic currents and on the so-called K(+)-depolarization in intact myelinated nerve fibres were studied. 4-AP, and in particular, Flaxedil, proved to be selective K(+)-current blockers. However, TEA, a crown ether (DCH18C6), a longchained triethylammonium compound (C10-TriEA), capsaicin, and the extract from the medicinal herb Ruta graveolens proved not to be selective K(+)-current blockers; they all block Na(+)-currents as well, although to a lesser extent. The sodium inactivation curve did not change under TEA and Flaxedil but was shifted on the potential axis in negative direction by DCH18C6, 4-AP, capsaicin and the Ruta extract whereas C10-TriEA caused a shift of both sodium inactivation and activation parameters in positive direction. Regarding to the kinetics of the persisting K(+)-current fraction, two different kinds of blockade were found: 1. Unchanged K(+)-kinetic which is typical for the effects of TEA, 4-AP, Flaxedil, and C10-TriEA. 2. Clearly changed K(+)-kinetic, characterized by K(+)-transients; which is typical for the effects of capsaicin and in particular, for those of DCH18C6 and of the Ruta extract. The possibly different modes of action of both groups of blockers are discussed in terms of current models for the action of potassium channel blockers.
Bethge
E W
EW
Department of Physiological Sciences, Valley University, Cali, Columbia.
Bohuslavizki
K H
KH
Hänsel
W
W
Kneip
A
A
Koppenhöfer
E
E
D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D002211:Capsaicin / Q000494:pharmacology; D043844:Crown Ethers; D004988:Ethers, Cyclic / Q000494:pharmacology; D005703:Gallamine Triethiodide / Q000494:pharmacology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D009186:Myelin Sheath / Q000187:drug effects* / Q000378:metabolism; D009474:Neurons / Q000187:drug effects / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D014982:Xenopus laevis
D043844:Crown Ethers; D004988:Ethers, Cyclic; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C002570:dicyclohexyl-18-crown-6; D019789:Tetraethylammonium; D015761:4-Aminopyridine; D005703:Gallamine Triethiodide; D002211:Capsaicin