title: Ionic mechanisms of action of GABA on dorsal and ventral root myelinated fibers: effects of K+ channel blockers.
abstract: Excitability changes evoked by the inhibitory neurotransmitter, GABA (gamma-aminobutyric acid) in myelinated axons of dorsal and ventral roots of the isolated bullfrog sciatic nerve were compared in the absence and presence of K+ channel blockers. Half-maximal A-fiber responses to a 0.5-Hz stimulation of the whole nerve were recorded from individual roots. Direct applications of Ringer with raised K+ levels to the site of stimulation caused increases in excitability of both dorsal and ventral root fibers, which resembled those evoked in the ventral root by the GABA agonist THIP (4,5,6,7-tetrahydroisoxazolo[5,4-c]ol). The increases in dorsal root fiber responses produced by GABA were depressed by tetraethylammonium (TEA) (3 mM), 4-aminopyridine (4-AP) (50 microM), Cs (2 mM), and Ba (1 mM). Ventral root fibers were less consistently affected. The early component of GABA-evoked excitability increases was depressed by 4-AP, Cs, and Ba, but greatly augmented by TEA. THIP-evoked changes in the excitability of the dorsal and ventral root fibers were, respectively, depressed and enhanced by TEA. The augmenting effect of TEA on the early component of GABA agonist effects on the ventral root fibers is attributed to their high resting K+ conductance and the presence of a slowly inactivating, fast K+ current (If1). The depressant effects of K+ channel blockade on depolarizing components of agonist-evoked changes in dorsal and ventral root responses indicate interference with release and (or) sensitivity to K+ and a possible contribution from a mechanism involving voltage-dependent delayed rectifier K+ currents.
authors.affiliation: Department of Anaesthesia, University of Toronto, Ont., Canada.
authors.forename: M E
authors.initials: ME
authors.lastname: Morris
authors.forename: S
authors.initials: S
authors.lastname: Liske
mesh_terms: D015761:4-Aminopyridine / Q000494:pharmacology; D000818:Animals; D001464:Barium / Q000494:pharmacology; D017609:Barium Compounds; D002586:Cesium / Q000494:pharmacology; D002712:Chlorides; D066298:In Vitro Techniques; D007555:Isoxazoles / Q000494:pharmacology; D009046:Motor Neurons / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D009475:Neurons, Afferent / Q000187:drug effects; D011188:Potassium / Q000494:pharmacology / Q000502:physiology; D015221:Potassium Channels / Q000187:drug effects*; D011892:Rana catesbeiana; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D005680:gamma-Aminobutyric Acid / Q000494:pharmacology*
chemical_list: D017609:Barium Compounds; D002712:Chlorides; D007555:Isoxazoles; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; C024986:barium chloride; D002586:Cesium; D001464:Barium; D005680:gamma-Aminobutyric Acid; D015761:4-Aminopyridine; C028019:cesium chloride; C015542:gaboxadol; D011188:Potassium