Effects of TRH on heteromeric rat erg1a/1b K+ channels are dominated by the rerg1b subunit.
The erg1a (HERG) K+ channel subunit and its N-terminal splice variant erg1b are coexpressed in several tissues and both isoforms have been shown to form heteromultimeric erg channels in heart and brain. The reduction of erg1a current by thyrotropin-releasing hormone (TRH) is well studied, but no comparable data exist for erg1b. Since TRH and TRH receptors are widely expressed in the brain, we have now studied the different TRH effects on the biophysical properties of homomeric rat erg1b as well as heteromeric rat erg1a/1b channels. The erg channels were overexpressed in the clonal somatomammotroph pituitary cell line GH3/B6, which contains TRH receptors and endogenous erg channels. Compared to rerg1a, homomeric rerg1b channels exhibited not only faster deactivation kinetics, but also considerably less steady-state inactivation, and half-maximal activation occurred at about 10 mV more positive potentials. Coexpression of both isoforms resulted in erg currents with intermediate properties concerning the deactivation kinetics, whereas rerg1a dominated the voltage dependence of activation and rerg1b strongly influenced steady-state inactivation. Application of TRH induced a reduction of maximal erg conductance for all tested erg1 currents without effects on the voltage dependence of steady-state inactivation. Nevertheless, homomeric rerg1b channels significantly differed in their response to TRH from rerg1a channels. The TRH-induced shift in the activation curve to more positive potentials, the dramatic slowing of activation and the acceleration of deactivation typical for rerg1a modulation were absent in rerg1b channels. Surprisingly, most effects of TRH on heteromeric rerg1 channels were dominated by the rerg1b subunit.
Kirchberger
Niklas M
NM
Institut für Angewandte Physiologie, Zentrum für Experimentelle Medizin, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, D-20246 Hamburg, Germany.
Wulfsen
Iris
I
Schwarz
Jürgen R
JR
Bauer
Christiane K
CK
D000200:Action Potentials; D000818:Animals; D002460:Cell Line; D000072237:ERG1 Potassium Channel; D004594:Electrophysiology; D051638:Ether-A-Go-Go Potassium Channels / Q000737:chemistry / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D005786:Gene Expression Regulation / Q000187:drug effects; D008564:Membrane Potentials / Q000187:drug effects; D010902:Pituitary Gland / Q000737:chemistry / Q000166:cytology; D020033:Protein Isoforms; D021122:Protein Subunits / Q000032:analysis / Q000502:physiology*; D051381:Rats; D018025:Receptors, Thyrotropin-Releasing Hormone / Q000032:analysis / Q000502:physiology; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology*
D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D020033:Protein Isoforms; D021122:Protein Subunits; D018025:Receptors, Thyrotropin-Releasing Hormone; D013973:Thyrotropin-Releasing Hormone