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

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