Effect of blocking hyperpolarization-activated cyclic nucleotidegated (HCN) channels on cough and bronchospasm in guinea pigs

Abstract

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..