Apamin-sensitive conductance mediates the K(+) current response during chemical ischemia in CA3 pyramidal cells.
Pyramidal cells typically respond to ischemia with initial transient hyperpolarization, which may represent a neuroprotective response. To identify the conductance underlying this hyperpolarization in CA3 pyramidal neurons of rat hippocampal organotypic slice cultures, recordings were obtained using the single-electrode voltage-clamp technique. Brief chemical ischemia (2 mM 2-deoxyglucose and 3 mM NaN(3), for 4 min) induced a response mediated by an increase in K(+) conductance. This current was blocked by intracellular application of the Ca(2+) chelator, bis-(o-aminophenoxy)-N,N,N', N'-tetraacetic acid (BAPTA), reduced with low external [Ca(2+)], and inhibited by a selective L-type Ca(2+) channel inhibitor, isradipine, consistent with the activation of a Ca(2+)-dependent K(+) conductance. Experiments with charybdotoxin (10 nM) and tetraethylammonium (TEA; 1 mM), or with the protein kinase C activator, phorbol 12,13-diacetate (PDAc; 3 microM), ruled out an involvement of a large conductance-type or an apamin-insensitive small conductance, respectively. In the presence of apamin (1 microM), however, the outward current was significantly reduced. These results demonstrate that in rat hippocampal CA3 pyramidal neurons an apamin-sensitive Ca(2+)-dependent K(+) conductance is activated in response to brief ischemia generating a pronounced outward current.
Tanabe
M
M
Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland.
Mori
M
M
Gähwiler
B H
BH
Gerber
U
U
D018528:ATP-Binding Cassette Transporters; D000818:Animals; D001030:Apamin / Q000494:pharmacology*; D002118:Calcium / Q000378:metabolism / Q000502:physiology; D002560:Cerebrovascular Circulation / Q000502:physiology; D018999:Charybdotoxin / Q000494:pharmacology; D002614:Chelating Agents / Q000494:pharmacology; D003847:Deoxyglucose; D004533:Egtazic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D006624:Hippocampus / Q000098:blood supply / Q000166:cytology / Q000378:metabolism*; D066298:In Vitro Techniques; D002546:Ischemic Attack, Transient / Q000139:chemically induced / Q000378:metabolism*; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; D017966:Pyramidal Cells / Q000187:drug effects / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D019810:Sodium Azide; D019789:Tetraethylammonium / Q000494:pharmacology
D018528:ATP-Binding Cassette Transporters; D002614:Chelating Agents; D054086:KATP Channels; D051036:Large-Conductance Calcium-Activated Potassium Channels; D015221:Potassium Channels; D024681:Potassium Channels, Calcium-Activated; D024661:Potassium Channels, Inwardly Rectifying; C092520:uK-ATP-1 potassium channel; D018999:Charybdotoxin; D001030:Apamin; D004533:Egtazic Acid; D019789:Tetraethylammonium; D019810:Sodium Azide; D003847:Deoxyglucose; C025603:1,2-bis(2-aminophenoxy)ethane-N,N,N',N'-tetraacetic acid; D002118:Calcium