Potassium channel blockade induces action potential generation in guinea-pig airway vagal afferent neurones.
Electrophysiological studies of vagal sensory nerves with cell bodies in the nodose ganglion and mechanically sensitive receptive fields in the guinea-pig trachea/bronchus, were performed. Exposure of the mechanically sensitive receptive fields to 4-aminopyridine (100 microM-1 mM) caused pronounced action potential discharge in all fibres studied. Action potential generation was also produced by alpha-dendrotoxin, and in a subset of fibres, by barium. By contrast, neither iberiotoxin, tetraethyl ammonium, glybenclamide, BDS-II, nor apamin caused action potential generation in the vagal afferent nerve fibres. Tetramethylrhodamine dextran was instilled into the trachea to retrogradely label cell bodies within the nodose ganglion. In these cells, 4-aminopyridine caused a large depolarization of the resting membrane potential, concomitant with an increase in input impedance. The data suggest 4-aminopyridine- and alpha-dendrotoxin-sensitive ion channels within the airway afferent nerve membrane hold the resting membrane potential below the threshold for action potential generation. Mechanisms that lead to an inhibition of these channels will likely lead to an increase in excitability of the airway afferent neurones.
McAlexander
M A
MA
Johns Hopkins Asthma and Allergy Center, Baltimore, MD 21224, USA.
Undem
B J
BJ
D015761:4-Aminopyridine / Q000494:pharmacology; D000200:Action Potentials / Q000187:drug effects* / Q000502:physiology*; D000344:Afferent Pathways / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D000818:Animals; D001980:Bronchi / Q000187:drug effects* / Q000294:innervation* / Q000378:metabolism; D006168:Guinea Pigs; D008297:Male; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D009412:Nerve Fibers / Q000187:drug effects / Q000378:metabolism / Q000648:ultrastructure; D009474:Neurons / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D009620:Nodose Ganglion / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism*; D026902:Potassium Channel Blockers; D015221:Potassium Channels / Q000187:drug effects* / Q000378:metabolism*
D026902:Potassium Channel Blockers; D015221:Potassium Channels; D015761:4-Aminopyridine