Strychnine‐induced potassium current in CA1 pyramidal neurones of the rat hippocampus

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Abstract
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 (VH) of − 20 mV, both Str and Bru elicited outward current at concentrations over 10−5 m. The reversal potential of Str-induced current (EStr) was − 77.8 mV, which was close to the K+ equilibrium potential (EK = − 80.3 mV). The change in EStr 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 × 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 × 10−4 m, respectively. 4 The Str-induced current (IStr) was antagonized by K+ channel blockers such as Ba2+, tetraethylammonium (TEA)-chloride, and 4-aminopyridine (4-AP) in a concentration-dependent manner. IStr was insensitive to glibenclamide, a blocker of ATP-sensitive K+ channels. 5 Internal perfusion with 10 mm BAPTA did not affect the Str-induced IK. 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 (GTPγS) and guanosine-5′-O-thiodiphosphate (GDPβS) suppressed the Str-induced IK, 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 Gi and/or Go might be involved in the Str-induced IK.