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 muM) had significant effects, omega-Conotoxin GVIA (0.5 muM) did not significantly affect firing of vagal mechanoreceptors. 4 In the majority of single units, 4-aminopyridine (4-AP) concentration-dependently (EC(50)similar to28 muM) 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 muM) increased stretch-induced firing, probably due to an increase in intramural tension. Glibenclamide (10 muM) 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.