MOLECULAR DETERMINANTS FOR ACTIVATION AND INACTIVATION OF HERG, A HUMAN INWARD RECTIFIER POTASSIUM CHANNEL

Citation
R. Schonherr et Sh. Heinemann, MOLECULAR DETERMINANTS FOR ACTIVATION AND INACTIVATION OF HERG, A HUMAN INWARD RECTIFIER POTASSIUM CHANNEL, Journal of physiology, 493(3), 1996, pp. 635-642
Citations number
18
Categorie Soggetti
Physiology
Journal title
ISSN journal
00223751
Volume
493
Issue
3
Year of publication
1996
Pages
635 - 642
Database
ISI
SICI code
0022-3751(1996)493:3<635:MDFAAI>2.0.ZU;2-E
Abstract
1. The human eag-related potassium channel, HERG, gives rise to inward ly rectifying K+ currents when expressed in Xenopus oocytes. 2. The ap parent inward rectification is caused by rapid inactivation. In extrac ellular Cs+ solutions, large outward currents can be recorded having a n inactivation time constant at 0 mV of about 50 ms with an e-fold cha nge every 37 mV. 3. HERG channel inactivation is not caused by an amin o-terminal ball structure, as a deletion of the cytoplasmic amino term inus (HERG Delta 2-373) did not eliminate inactivation. However, chann el deactivation was accelerated about 12-fold at -80 mV. 4. Mutation o f S631 to A, the homologous residue of eag channels, in the outer mout h of the HERG pore completely abolished channel inactivation. 5. Activ ity of HERG channels depended on extracellular cations, which are effe ctive for channel activation, in the order Cs+>K(+)much greater than L i+>Na+. The point mutation S631A strong ly reduced this channel regula tion. 6. By analogy to functional aspects of cloned voltage-gated pota ssium channels, rectification of HERG, as well as its kinetic properti es during the course of an action potential, are presumably governed b y a mechanism reminiscent of C-type inactivation.