Ethanol increases the activity of large conductance, Ca(2+)-activated K+ channels in isolated neurohypophysial terminals.
Large conductance, Ca(2+)-activated K+ channels are believed to underlie interburst intervals and, thus, contribute to the control of hormone release from neurohypophysial terminals. Because ethanol inhibits the release of vasopressin and oxytocin, we studied its effects on large conductance, Ca(2+)-activated K+ channels from these terminals using patch-clamp techniques. Ethanol (10-100 mM) applied to the cytosolic surface of excised, inside-out patches reversibly increases channel activity in a concentration-dependent manner, reaching a plateau at 50-100 mM. This activation is not mediated by freely diffusible cytosolic second messengers or the release of Ca2+ from intracellular stores. Rather, it likely reflects a direct interaction of ethanol with the channel protein or a closely associated component. Neither the unitary conductance nor the characteristics of the voltage-current relationship are modified by the drug. The increase of channel activity by ethanol results from a modification of channel gating properties: the contribution of long openings to the total time spent in the open state is increased, the average duration of the fast openings is slightly increased, and long closures disappear in the presence of the drug. The activation of large conductance, Ca(2+)-activated K+ channels by ethanol, in conjunction with the previously reported inhibition of voltage-dependent Ca2+ channels, can explain the reduced release of vasopressin and oxytocin after ethanol ingestion.
Dopico
A M
AM
Department of Pharmacology and Molecular Toxicology, University of Massachusetts Medical School, Worcester 01655, USA.
Lemos
J R
JR
Treistman
S N
SN
D000818:Animals; D002118:Calcium / Q000494:pharmacology*; D000431:Ethanol / Q000494:pharmacology*; D015640:Ion Channel Gating; D017136:Ion Transport; D008297:Male; D010902:Pituitary Gland / Q000187:drug effects* / Q000502:physiology; D011188:Potassium / Q000378:metabolism; D015221:Potassium Channels / Q000187:drug effects* / Q000502:physiology; D017729:Presynaptic Terminals / Q000187:drug effects* / Q000502:physiology; D051381:Rats
D015221:Potassium Channels; D000431:Ethanol; D011188:Potassium; D002118:Calcium