Baclofen activates voltage-dependent and 4-aminopyridine sensitive K+ conductance in guinea-pig hippocampal pyramidal cells maintained in vitro.
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 -95mV. 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 X 10(-6) M) whereas it was unaffected by picrotoxin (2 X 10(-5) M). These results strongly suggest that the effect of baclofen is mediated by an increase in K+ conductance.
Inoue
M
M
Matsuo
T
T
Ogata
N
N
D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology*; D000818:Animals; D001418:Baclofen / Q000494:pharmacology*; D002712:Chlorides / Q000378:metabolism; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D006168:Guinea Pigs; D006624:Hippocampus / Q000187:drug effects* / Q000502:physiology; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects; D011188:Potassium / Q000378:metabolism* / Q000494:pharmacology; D013757:Tetraethylammonium Compounds / Q000494:pharmacology
D000631:Aminopyridines; D002712:Chlorides; D013757:Tetraethylammonium Compounds; D015761:4-Aminopyridine; D001418:Baclofen; D011188:Potassium