HCN channel blockers increase parasympathetic ganglionic transmission in guinea pig airways

Abstract

Hyperpolarization activated cyclic nucleotide gated (HCN) channels regulate neuronal membrane potential. We assessed whether HCN channel blockers (ZD7288 or Cs+) alter vagal control of airway smooth muscle. In anaesthetized, ventilated guinea pigs bilateral electrical stimulation (32Hz, 10 sec) of the vagi produced voltage dependent (1‐12V), atropine sensitive airway contractions. The voltage producing 50% maximum contraction was reduced from 6.0±0.7 in vehicle (n=6) to 3.3±0.7 in ZD7288 (2mg/kg, iv, n=7) treated animals, P<0.05. Vagus nerve‐evoked contractions in vitro were potentiated by 5mM Cs+ (n=8). At stimulus intensities of 10.3±1.3 volts, t..