4-aminopyridine- and dendrotoxin-sensitive potassium channels influence excitability of vagal mechano-sensitive endings in guinea-pig oesophagus

4-氨基吡啶和树突状毒素敏感钾通道影响豚鼠食管迷走神经机械敏感末梢的兴奋性

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作者:Vladimir P Zagorodnyuk, Bao Nan Chen, Marcello Costa, Simon J H Brookes

Abstract

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.

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