K+-channel blockade in trigeminal root ganglion neurons: effects on membrane outward currents.
1. The effects of the applications of three K+-channel blockers on the membrane outward currents of neurons were studied with single-electrode voltage-clamp techniques in in vitro slice preparations of the trigeminal root ganglion (TRG) of guinea pigs. The investigations are the first reported attempts to apply these techniques to TRG neurons. 2. During perfusion with tetrodotoxin (TTX; 1 microM), transient outward currents were elicited at the termination of hyperpolarizing voltage commands from holding potentials near -40 mV. The amplitudes of these currents were reduced in conditions of high extracellular [K+]. The activation of such currents was rapid (less than 5 ms), and inactivation was complete at potentials within the activation range. Perfusion with low-[Ca2+], Co2+-containing solutions only slightly and inconsistently reduced the transient outward currents. 3. During combined application of TTX (1 microM) and tetraethylammonium (TEA) (10 mM), fast-activating sustained currents (greater than 1 s) were evoked by depolarizing commands from holding potentials near -70 mV. These currents were blocked completely by the additional inclusion of 5 mM 4-aminopyridine (4-AP) in the perfusing solution. 4. Applications of TEA (0.1-10 mM) produced dose-dependent reductions in the amplitudes of the transient outward currents. Applications of Cs+ also greatly reduced the currents. However, administrations of 4-AP (50 microM-5 mM) diminished these currents only slightly, and high doses of muscarinic agonists had no effect.(ABSTRACT TRUNCATED AT 250 WORDS)
Spigelman
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Department of Pharmacology and Therapeutics, Faculty of Medicine, University of British Columbia, Vancouver, Canada.
Puil
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D015761:4-Aminopyridine; D000631:Aminopyridines / Q000494:pharmacology; D000818:Animals; D002462:Cell Membrane / Q000502:physiology; D002586:Cesium / Q000494:pharmacology; D002800:Cholinesterase Inhibitors / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D006168:Guinea Pigs; D008564:Membrane Potentials / Q000187:drug effects; D009474:Neurons / Q000187:drug effects*; D010277:Parasympathomimetics / Q000494:pharmacology; D015221:Potassium Channels / Q000187:drug effects*; D019789:Tetraethylammonium; D013757:Tetraethylammonium Compounds / Q000494:pharmacology; D013779:Tetrodotoxin / Q000494:pharmacology; D012668:Trigeminal Ganglion / Q000166:cytology*; D014276:Trigeminal Nerve / Q000166:cytology*
D000631:Aminopyridines; D002800:Cholinesterase Inhibitors; D010277:Parasympathomimetics; D015221:Potassium Channels; D013757:Tetraethylammonium Compounds; D002586:Cesium; D013779:Tetrodotoxin; D019789:Tetraethylammonium; D015761:4-Aminopyridine