RT Journal Article
SR Electronic
T1 Effects of bretylium tosylate on voltage-gated potassium channels in human T lymphocytes.
JF Molecular Pharmacology
JO Mol Pharmacol
FD American Society for Pharmacology and Experimental Therapeutics
SP 762
OP 766
VO 46
IS 4
A1 R Gáspár, Jr
A1 G Panyi
A1 D L Ypey
A1 Z Krasznai
A1 G Vereb
A1 C Pieri
A1 S Damjanovich
YR 1994
UL http://molpharm.aspetjournals.org/content/46/4/762.abstract
AB Using the patch-clamp technique, we determined that bretylium tosylate, a quaternary ammonium compound possessing immunomodulating activity, decreased the whole-cell K+ current in human T lymphocytes, in a dose-dependent manner, in the 0.05-5 mM extracellular concentration range. Bretylium tosylate prolonged the recovery from inactivation and accelerated the inactivation and deactivation of the K+ current but did not influence the kinetics of activation or the voltage dependence of activation and steady state inactivation of the K+ conductance. The percentage of drug-induced block was independent of membrane potential. K+ channel block by bretylium tosylate was partially and slowly removable by washing with drug-free extracellular solution. Bovine serum albumin (10 mg/ml) in the bath lifted the drug-induced block almost instantaneously, although not completely. In control experiments bovine serum albumin increased the inactivation time constant of the K+ channels but left the peak K+ current amplitude unaffected. On the basis of the experimental evidence, a gating-dependent allosteric interaction is suggested for the mechanism of drug action. The effective dose range, time of exposure, and reversibility of bretylium tosylate-induced K+ channel block correlated well with the same parameters of the drug-induced inhibition of T lymphocyte activation. The reported effects of bretylium tosylate on T cell mitogenesis can be regarded partly as a consequence of its blocking effects on voltage-gated K+ channels.