Isolation of a long-lasting eag-related gene-type K+ current in MMQ lactotrophs and its accommodating role during slow firing and prolactin release.
Native rat lactotrophs express thyrotrophin-releasing hormone-dependent K+ currents consisting of fast and slow deactivating components that are both sensitive to the class III anti-arrhythmic drugs that block the eag-related gene (ERG) K+ current (I(ERG)). Here we describe in MMQ prolactin-releasing pituitary cells the isolation of the slowly deactivating long-lasting component (I(ERGS)), which, unlike the fast component (I(ERGF)), is insensitive to verapamil 2 microm but sensitive to a novel scorpion toxin (ErgTx-2) that hardly affects I(ERGF). The time constants of I(ERGS) activation, deactivation, and recovery from inactivation are more than one order of magnitude greater than in I(ERGF), and the voltage-dependent inactivation is left-shifted by approximately 25 mV. The very slow MMQ firing frequency (approximately 0.2 Hz) investigated in perforated patch is increased approximately four times by anti-arrhythmic agents, by ErgTx-2, and by the abrupt I(ERGS) deactivation. Prolactin secretion in the presence of anti-arrhythmics is three- to fourfold higher in comparison with controls. We provide evidence from I(ERGS) and I(ERGF) simulations in a firing model cell to indicate that only I(ERGS) has an accommodating role during the experimentally observed very slow firing. Thus, we suggest that I(ERGS) potently modulates both firing and prolactin release in lactotroph cells.
Lecchi
Marzia
M
Department of Biotechnology and Biosciences, University of Milano-Bicocca, I-20126 Milano, Italy.
Redaelli
Elisa
E
Rosati
Barbara
B
Gurrola
Georgina
G
Florio
Tullio
T
Crociani
Olivia
O
Curia
Giulia
G
Cassulini
Rita Restano
RR
Masi
Alessio
A
Arcangeli
Annarosa
A
Olivotto
Massimo
M
Schettini
Gennaro
G
Possani
Lourival D
LD
Wanke
Enzo
E
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D000889:Anti-Arrhythmia Agents / Q000494:pharmacology; D001921:Brain / Q000378:metabolism; D002121:Calcium Channel Blockers / Q000494:pharmacology; D027682:Cation Transport Proteins; D002460:Cell Line; D003198:Computer Simulation; D004305:Dose-Response Relationship, Drug; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; D026901:Membrane Transport Proteins; D008959:Models, Neurological; D018408:Patch-Clamp Techniques; D010902:Pituitary Gland / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D011188:Potassium / Q000378:metabolism*; D015221:Potassium Channels / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D024642:Potassium Channels, Voltage-Gated; D011388:Prolactin / Q000378:metabolism*; D012313:RNA / Q000235:genetics / Q000378:metabolism; D051381:Rats; D012604:Scorpion Venoms / Q000302:isolation & purification / Q000494:pharmacology; D014212:Tretinoin / Q000378:metabolism; D014700:Verapamil / Q000494:pharmacology
D000889:Anti-Arrhythmia Agents; D002121:Calcium Channel Blockers; D027682:Cation Transport Proteins; D000072237:ERG1 Potassium Channel; D051638:Ether-A-Go-Go Potassium Channels; 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; D012604:Scorpion Venoms; D014212:Tretinoin; D012313:RNA; D011388:Prolactin; D014700:Verapamil; D011188:Potassium