The Journal of Neurophysiology Vol. 82 No. 6 December 1999, pp. 2876-2882
Copyright ©1999 by the American Physiological Society

Apamin-Sensitive Conductance Mediates the K⁺ Current Response During Chemical Ischemia in CA3 Pyramidal Cells

Brain Research Institute, University of Zurich, CH-8057 Zurich, Switzerland

Tanabe, Mitsuo, Masahiro Mori, Beat H. Gähwiler, and Urs Gerber. Apamin-Sensitive Conductance Mediates the K⁺ Current Response During Chemical Ischemia in CA3 Pyramidal Cells. J. Neurophysiol. 82: 2876-2882, 1999. 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 NaN₃, for 4 min) induced a response mediated by an increase in K⁺ conductance. This current was blocked by intracellular application of the Ca²⁺ chelator, bis-(o-aminophenoxy)-N,N,N',N'-tetraacetic acid (BAPTA), reduced with low external [Ca²⁺], and inhibited by a selective L-type Ca²⁺ channel inhibitor, isradipine, consistent with the activation of a Ca²⁺-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 µM), ruled out an involvement of a large conductance-type or an apamin-insensitive small conductance, respectively. In the presence of apamin (1 µM), however, the outward current was significantly reduced. These results demonstrate that in rat hippocampal CA3 pyramidal neurons an apamin-sensitive Ca²⁺-dependent K⁺ conductance is activated in response to brief ischemia generating a pronounced outward current.