STRYCHNINE-INDUCED POTASSIUM CURRENT IN CA1 PYRAMIDAL NEURONS OF THE RAT HIPPOCAMPUS

1 Direct actions of strychnine (Str) and brucine (Bru) on the dissociated hippocampal CA1 neurones of the rat have been investigated with the whole-cell mode of the patch-clamp technique. 2 At a holding potential (V(H)) of - 20 mV, both Str and Bru elicited outward current at concentrations over 10(-5) M. The reversal potential of Str-induced current (E(Str)) was - 77.8 mV, which was close to the K+ equilibrium potential (E(K) = - 80.3 mV). The change in E(Str) for a ten fold change in extracellular K+ concentration was 58 mV, indicating that the membrane behaves like a K+ electrode in the presence of Str. 3 The concentration-response curves for Str and Bru were bell-shaped, and nearly maximum response occurred at 10(-4) M for Str and 3 X 10(-4) M for Bru. The maximum current amplitude induced by Bru was about 80% of that induced by Str. A transient 'hump' current appeared immediately after the wash-out of external solutions containing Str and Bru at concentrations higher than 10(-4) and 3 X 10(-4) M, respectively. 4 The Str-induced current (I(Str)) was antagonized by K+ channel blockers such as Ba2+, tetraethyl-ammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. I(Str) was insensitive to glibenclamide, a blocker of ATP-sensitive K+ channels. 5 Internal perfusion with 10 mM BAPTA did not affect the Str-induced I(K). Depletion of the intracellular Ca2+ store by caffeine had no effect, indicating that intracellular Ca2+ does not mediate the Str-induced activation of K+ conductance. 6 Both guanosine-5'-O-3-thiotriphosphate (GTP-gamma-S) and guanosine-5'-O-thiodiphosphate (GDP-beta-S) suppressed the Str-induced I(K), the former action appearing more rapidly than the latter. The results suggest that the GTP binding proteins are involved in this Str response. 7 When neurones were loaded with cholera toxin (CTX) or pertussis toxin (PTX) through a patch pipette, PTX suppressed the Str response whereas CTX did not, suggesting that G(i) and/or G(o) might be involved in the Str-induced I(K).