HERG K(+) currents in human prolactin-secreting adenoma cells.
To investigate the presence and possible function of ether-à-go-go-related gene (erg) K(+) channels in human lactotroph cells (HERG channels), primary cultures were prepared from human prolactinoma tissue. In almost all primary cultures, HERG currents could be recorded in identified prolactin cells using an external high-K(+) solution. The antiarrhythmic agent E-4031, a specific blocker of erg channels, served to isolate HERG currents as the drug-sensitive currents. In cells of two tumours tested, thyrotropin-releasing hormone significantly reduced the amplitude of the HERG currents. The potential dependence of HERG current availability and the deactivation kinetics differed significantly even between prolactin cells derived from one adenoma. For comparison, corresponding values were obtained for heterologously expressed rat erg1, erg2 and erg3 channels. The expression of the three HERG channel subunits was investigated in nine human adenomas using RT-PCR. Transcripts for HERG1 were present in all adenomas and although transcripts for HERG2 and HERG3 were also detected, their expression level was more variable. The results demonstrate the functional expression of HERG channels in human prolactin-secreting tumours and are compatible with a physiological role for these channels in the control of prolactin secretion, as has been shown in normal rat lactotroph cells.
Bauer
C K
CK
Institut für Angewandte Physiologie, Universitätsklinikum Hamburg-Eppendorf, Martinistrasse 52, Universität Hamburg, 20246 Hamburg, Germany. c.bauer@uke.uni-hamburg.de
Wulfsen
I
I
Schäfer
R
R
Glassmeier
G
G
Wimmers
S
S
Flitsch
J
J
Lüdecke
D K
DK
Schwarz
J R
JR
D000818:Animals; D016466:CHO Cells; D027682:Cation Transport Proteins; D006224:Cricetinae; D004268:DNA-Binding Proteins; D000072237:ERG1 Potassium Channel; D004553:Electric Conductivity; D051638:Ether-A-Go-Go Potassium Channels; D006801:Humans; D008564:Membrane Potentials / Q000187:drug effects; D026901:Membrane Transport Proteins; D010911:Pituitary Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D024642:Potassium Channels, Voltage-Gated; D015175:Prolactinoma / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000494:pharmacology; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; D014407:Tumor Cells, Cultured
D027682:Cation Transport Proteins; D004268:DNA-Binding Proteins; C072312:ERG protein, human; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; C418492:KCNE3 protein, human; C000606913:KCNH2 protein, human; C092509:KCNH6 protein, human; C486376:KCNH7 protein, human; C109500:Kcnh6 protein, rat; C109501:Kcnh7 protein, rat; D026901:Membrane Transport Proteins; D015221:Potassium Channels; D024642:Potassium Channels, Voltage-Gated; D015534:Trans-Activators; D000071230:Transcriptional Regulator ERG; C059983:potassium channel protein I(sk); D013973:Thyrotropin-Releasing Hormone