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

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Abstract
The ionic mechanism underlying the effect of (—)‐baclofen in the hippocampus was investigated using guinea‐pig brain slices. (—)‐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. The value of the reversal potential for the baclofen‐induced hyperpolarization, as estimated from the current‐voltage relationships, was about −95 mV. 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. 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. 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). These results strongly suggest that the effect of baclofen is mediated by an increase in K+ conductance.