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001-es BibID:	BIBFORM004726
Első szerző:	Hajdu Péter (biofizikus)
Cím:	Drug- and mutagenesis-induced changes in the selectivity filter of a cardiac two-pore background K+ channel / Péter Hajdú, Chris Ulens, György Panyi, Jan Tytgat
Dátum:	2003
ISSN:	008-6363 (Print)
Megjegyzések:	As compared with voltage-gated K(+) channels (Kv-type), our knowledge of the structure-function and pharmacology of two-pore background K(+) channels is still very limited. Here we have used a drug- and mutagenesis-based approach to study the effect of the antidepressant fluoxetine (FL) and analgesic D-norpropoxyphene (NORP) on the cardiac two-pore background K(+) channel. METHODS: Whole-cell currents of the cTBAK-1 channel expressed in Xenopus laevis oocytes were investigated using conventional two-microelectrode voltage-clamp recording method combined with functional mutagenesis of the channel protein. RESULTS: Both drugs inhibit cTBAK-1 current: FL proved to be a voltage-dependent pore-blocker, while NORP induced a change in the selectivity of cTBAK-1 giving rise to a shift in the reversal potential (E(rev)) toward more positive voltages due to an increased Na(+) permeability. Mutations were introduced into the selectivity filter of the first (Y105F) and the second (F211Y) pore to mimic the P-region of HERG (GFGN) and Kv1.1 (GYGD) channels. Point mutations in the channel resulted in two distinct phenotypes of cTBAK-1: the mutant Y105F channel lost its selectivity and was unaffected by NORP, in contrast to the F211Y mutant. CONCLUSION: FL and NORP block the current of cTBAK-1 channels differently, the latter modified the selectivity of the channel pore. Our mutagenesis study revealed that NORP interacts with the selectivity filter of cTBAK-1. The significant role of the GYGD motif in this type of K(+) channels is emphasized
Tárgyszavak:	Orvostudományok Elméleti orvostudományok idegen nyelvű folyóiratközlemény külföldi lapban Amino Acid Motifs Analgesics analogs and derivatives Animals Antidepressive Agents Biophysics drug effects Female Fluoxetine genetics Hungary Ion Channels metabolism methods Mice Mutagenesis, Site-Directed Mutation Oocytes pharmacology Phenotype Point Mutation Potassium Potassium Channels Tandem Pore Domain Propoxyphene Research Sodium Support Transcription Xenopus laevis
Megjelenés:	Cardiovascular Research. - 58 : 1 (2003), p. 46-54. -
További szerzők:	Ulens, Chris Panyi György (1966-) (biofizikus) Tytgat, Jan
Internet cím:	DOI Intézményi repozitóriumban (DEA) tárolt változat
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