Hyperpolarization-activated current, Ih, in inspiratory brainstem neurons and its inhibition by hypoxia

A hyperpolarization-activated current, Ih, is often implied in pacemaker-like depolarizations during rhythmic oscillatory activity. We describe Ih in the isolated respiratory centre of immature mice (P6-P11). Ih was recorded in 15% (22/146) of all inspiratory neurons examined. The mean half-maximal Ih activation occurred at -78 mV and the reversal potential was -40 mV. Ih was inhibited by Cs+ (1-5 mM) and by organic blockers N-ethyl-1,6-dihydro-1, 2-dimethyl-6-(methylimino)-N-phenyl-4-pyrimidinamine (ZD 7288; 0.3-3 microM) and N,N'-bis-(3,4-dimethylphenylethyl)-N-methylamine (YS 035, 3-30 microM), but not by Ba2+ (0.5 mM). The organic Ih blockers did not change the inspiratory bursts recorded from the XIIth nerve and synaptic drives in inspiratory neurons. Hypoxia reversibly inhibited Ih but, in the presence of organic blockers, the hypoxic reaction remained unchanged. We conclude that although Ih channels are functional in a minority of inspiratory neurons, Ih does not contribute to respiratory rhythm generation or its modulation by hypoxia.