Baclofen activates voltage‐dependent and 4‐aminopyridine sensitive K+ conductance in guinea‐pig hippocampal pyramidal cells maintained in vitro

Abstract

1 The ionic mechanism underlying the effect of (—)-baclofen in the hippocampus was investigated using guinea-pig brain slices. 2 (—)-Baclofen either perfused or applied directly by microiontophoresis hyperpolarized the membrane and decreased the membrane input resistance of pyramidal cells in a dose-dependent manner. 3 The value of the reversal potential for the baclofen-induced hyperpolarization, as estimated from the current-voltage relationships, was about −95 mV. 4 The reversal potential of the baclofen-induced hyperpolarization measured directly coincided with that for the post-burst hyperpolarization which is known to result from an activation of Ca²⁺-activated K⁺ conductance. 5 The amplitude of the baclofen-induced hyperpolarization was increased in low K⁺ (1.24 mm) medium whereas the hyperpolarization was decreased or abolished in high K⁺ (12.4 and 25 mm). Low Cl⁻ (10.2 mm) medium had no noticeable effect on the baclofen-induced hyperpolarization. 6 The effect of baclofen was antagonized by a low dose of 4-aminopyridine (5 × 10⁻⁶ m) whereas it was unaffected by Picrotoxin (2 × 10⁵m). 7 These results strongly suggest that the effect of baclofen is mediated by an increase in K⁺ conductance.