4-aminopyridine- and dendrotoxin-sensitive potassium channels influence excitability of vagal mechano-sensitive endings in guinea-pig oesophagus.
1. Distension-sensitive vagal afferent fibres from the guinea-pig oesophagus were recorded extracellularly in vitro. Most recorded units were spontaneously active firing at 3.2+/-0.3 Hz (n=41, N=41) and had low thresholds (less than 1 mm) to circumferential stretch. Dynamic and adapted phases of stretch-evoked firing, as well as a silent period were linearly dependent on the amplitude of stretch. 2. High K+ (7-12 mM) Krebs solution dose-dependently increased both spontaneous and stretch-evoked firing and reduced the duration of the silent period. 3. Charybdotoxin (ChTX, 100 nM) slightly increased spontaneous and stretch-evoked firing and decreased the silent period, while neither iberiotoxin (100 nM) nor apamin (0.5 microM) had significant effects. omega-Conotoxin GVIA (0.5 microM) did not significantly affect firing of vagal mechanoreceptors. 4. In the majority of single units, 4-aminopyridine (4-AP) concentration-dependently (EC(50) approximately 28 microM) increased spontaneous firing, strongly reduced the silent period but did not affect stretch (3 mm)-induced firing. Firing evoked by 1-2 mm was increased by 4-AP. 5. Alpha-dendrotoxin (DnTX, 300 nM) and DnTX K (30 nM) slightly increased spontaneous and stretch-evoked firing. There was no additive effect on spontaneous firing when ChTX and DnTX K were applied simultaneously. 6. Barium (100 microM) increased stretch-induced firing, probably due to an increase in intramural tension. Glibenclamide (10 microM) had no effect on spontaneous or stretch-induced firing. 7. The results indicate that voltage-gated 4-AP- and dendrotoxin-sensitive K+ channels are the main type of K+ channels that influence excitability of vagal mechano-sensitive endings of the guinea-pig oesophagus. They were involved in control of spontaneous firing and in stretch-induced firing evoked by moderate stretch, but none of the K+ channels appeared to be involved in adaptation to maintained stretch by their slowly adapting vagal mechanoreceptors.
Zagorodnyuk
Vladimir P
VP
Department of Human Physiology and Centre for Neuroscience, Flinders University, GPO Box 2100, Adelaide, South Australia, Australia. vladimir.zagorodnyuk@flinders.edu.au
Chen
Bao Nan
BN
Costa
Marcello
M
Brookes
Simon J H
SJ
D015761:4-Aminopyridine / Q000494:pharmacology*; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004546:Elapid Venoms / Q000494:pharmacology*; D004947:Esophagus / Q000187:drug effects* / Q000502:physiology; D005260:Female; D006168:Guinea Pigs; D008297:Male; D008465:Mechanoreceptors / Q000187:drug effects / Q000502:physiology; D026902:Potassium Channel Blockers / Q000494:pharmacology*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D014630:Vagus Nerve / Q000187:drug effects* / Q000502:physiology
D004546:Elapid Venoms; D026902:Potassium Channel Blockers; D015221:Potassium Channels; C020273:dendrotoxin; D015761:4-Aminopyridine