Inhibition of BK channels contributes to the second phase of the response to TRH in clonal rat anterior pituitary cells.
OBJECTIVE
Thyrotropin-releasing hormone (TRH) induces biphasic changes in the electrical activity, the cytosolic free Ca2+ concentration ([Ca2+]i), and prolactin secretion from both GH cells and native lactotrophs. It is well established that inhibition of erg channels contributes to the second phase of the TRH response. We have investigated if BK channels are also involved.


RESULTS
The BK channels may be active at the resting membrane potential (open probability, Po=0.01) in clonal rat anterior pituitary cells (GH4), which makes it possible that inhibition of these channels may contribute to the reduced K+ conductance during the TRH response. The specific BK channel blocker iberiotoxin (IbTx, 100 nm) had no effect on the resting conductance at holding potentials negative to -40 mV, but significantly reduced the conductance at shallower membrane potentials. This corresponds to the voltage dependency of the sustained [Ca2+]i. Furthermore, IbTx increased the action potential frequency by 36% in spontaneously firing cells. During the second phase of the TRH response, the action potential frequency increased by 34%, concomitantly with 61% reduction of the Po of single BK channels. The protein kinase C (PKC)-activating phorbol ester TPA had no significant effect on BK channel Po within the normal range of the resting potential.


CONCLUSIONS
The BK channels may contribute to the resting membrane conductance, and they are partially inhibited by TRH during the second phase. This modulation seems not to depend on PKC. We propose that inhibition of erg and BK channels acts in concert to enhance the cell excitability during the second phase of the response to TRH.
Haug
T M
TM
Department of Biology, University of Oslo, Oslo, Norway.
Hafting
T
T
Sand
O
O
D000200:Action Potentials / Q000187:drug effects; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002460:Cell Line; D003592:Cytophotometry / Q000379:methods; D020536:Enzyme Activators / Q000494:pharmacology; D051036:Large-Conductance Calcium-Activated Potassium Channels; D008564:Membrane Potentials / Q000187:drug effects; D010455:Peptides / Q000494:pharmacology; D010703:Phorbol Esters / Q000494:pharmacology; D010903:Pituitary Gland, Anterior / Q000166:cytology* / Q000187:drug effects; D011188:Potassium / Q000378:metabolism; D026902:Potassium Channel Blockers / Q000494:pharmacology; D024681:Potassium Channels, Calcium-Activated / Q000502:physiology*; D011493:Protein Kinase C / Q000378:metabolism; D051381:Rats; D013973:Thyrotropin-Releasing Hormone / Q000502:physiology*
D020536:Enzyme Activators; D051036:Large-Conductance Calcium-Activated Potassium Channels; D010455:Peptides; D010703:Phorbol Esters; D026902:Potassium Channel Blockers; D024681:Potassium Channels, Calcium-Activated; D013973:Thyrotropin-Releasing Hormone; C064719:iberiotoxin; D011493:Protein Kinase C; D011188:Potassium; D002118:Calcium