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Thoby-Brisson M, Telgkamp P, Ramirez JM: The role of the hyperpolarization-activated current in modulating rhythmic activity in the isolated respiratory network of mice. J Neurosci. 2000 Apr 15;20(8):2994-3005.
We examined the role of the hyperpolarization-activated current (I (h)) in the generation of the respiratory rhythm using a spontaneously active brainstem slice of mice. This preparation contains the hypoglossus (XII) nucleus, which is activated in-phase with inspiration and the pre-Botzinger complex (PBC), the presumed site for respiratory rhythm generation. Voltage-clamp recordings (n = 90) indicate that cesium (Cs) (5 mM) blocked 77.2% of the I (h) current, and ZD 7288 (100 microM) blocked 85.8% of the I (h) current. This blockade increased the respiratory frequency by 161% in Cs and by 150% in ZD 7288 and increased the amplitude of integrated population activity in the XII by 97% in Cs and by 162% in ZD 7288, but not in the PBC (Cs, by 19%; ZD 7288, by -4.56%). All inspiratory PBC neurons (n = 44) recorded in current clamp within the active network revealed a significantly decreased frequency of action potentials during the interburst interval and an earlier onset of inspiratory bursts after I (h) current blockade. However, hyperpolarizing current pulses evoked only in a small proportion of inspiratory neurons (0% of type I; 29% of type II neurons) a depolarizing sag. Most of the neurons expressing an I (h) current (86%) were pacemaker neurons, which continued to generate rhythmic bursts after inactivating the respiratory network pharmacologically with CNQX alone or with CNQX, AP-5, strychnine, bicuculline, and carbenoxolone. Cs and ZD 7288 increased the frequency of pacemaker bursts and decreased the frequency of action potentials between pacemaker bursts. Our findings suggest that the I (h) current plays an important role in modulating respiratory frequency, which is presumably mediated by pacemaker neurons. |
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