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4‐aminopyridine‐ and dendrotoxin‐sensitive potassium channels influence excitability of vagal mechano‐sensitive endings in guinea‐pig oesophagus
Author(s) -
Zagorodnyuk Vladimir P,
Chen Bao Nan,
Costa Marcello,
Brookes Simon J H
Publication year - 2002
Publication title -
british journal of pharmacology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.432
H-Index - 211
eISSN - 1476-5381
pISSN - 0007-1188
DOI - 10.1038/sj.bjp.0704964
Subject(s) - charybdotoxin , apamin , 4 aminopyridine , iberiotoxin , chemistry , potassium channel , biophysics , anatomy , anesthesia , medicine , biology
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. High K + (7–12 m M ) Krebs solution dose‐dependently increased both spontaneous and stretch‐evoked firing and reduced the duration of the silent period. Charybdotoxin (ChTX, 100 n M ) slightly increased spontaneous and stretch‐evoked firing and decreased the silent period, while neither iberiotoxin (100 n M ) nor apamin (0.5 μ M ) had significant effects. ω‐Conotoxin GVIA (0.5 μ M ) did not significantly affect firing of vagal mechanoreceptors. In the majority of single units, 4‐aminopyridine (4‐AP) concentration‐dependently (EC 50 ∼28 μ M ) 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. α‐Dendrotoxin (DnTX, 300 n M ) and DnTX K (30 n M ) slightly increased spontaneous and stretch‐evoked firing. There was no additive effect on spontaneous firing when ChTX and DnTX K were applied simultaneously. Barium (100 μ M ) increased stretch‐induced firing, probably due to an increase in intramural tension. Glibenclamide (10 μ M ) had no effect on spontaneous or stretch‐induced firing. 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.British Journal of Pharmacology (2002) 137 , 1195–1206. doi: 10.1038/sj.bjp.0704964