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
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.