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Effect of blocking hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels on cough and bronchospasm in guinea pigs
Author(s) -
Mazzone Stuart B,
McGovern Alice E,
Carr Michael J,
McAlexander M Allen
Publication year - 2007
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.21.6.a959-d
Subject(s) - cough reflex , chemistry , anesthesia , capsaicin , bronchospasm , stimulation , histamine , reflex , pharmacology , medicine , endocrinology , asthma , biochemistry , receptor
HCN channels play a role in regulating the excitability of a variety of somatic and visceral sensory nerves. We set out to test whether blocking HCN channels in the airways with either cesium chloride (CsCl) or ZD7288 modifies the cough reflex or bronchospasm in urethane‐anesthetized guinea pigs. Cough was evoked in spontaneously breathing animals from an isolated segment of trachea using either bolus application of citric acid (1–2000mM) or electrical stimulation (1–12 volts/16Hz/10sec trains). Topical application of 5mM CsCl significantly (P<0.05) inhibited citric acid‐evoked cough, but paradoxically reduced the threshold for electrically‐evoked cough. Prior treatment with prostaglandin E2 or ovalbumin sensitization and challenge did not modify the cough reflex. In mechanically ventilated guinea pigs, intravenous injection of histamine (0.5–20ug/kg) or capsaicin (0.5–20ƒÝg/kg) dose‐dependently increased inflation pressure which was significantly potentiated by ZD7288 (2–10mg/kg). Nerve fiber recordings revealed differential effects of CsCl on the excitability of identified airway vagal afferents. These data suggest that HCN channels play multiple roles in the regulation of airway function.