Characterization of a hyperpolarization-activated inward current in rat chemosensory petrosal neurons in vitro

Abstract

Regulation of carotid body chemoafferent discharge in mammals plays an important role in the reflex control of ventilation. A non-selective blocker (cesium) of the inward rectifier is known to inhibit carotid body afferent discharge during hypoxia, but the underlying current in corresponding neurons of the petrosal ganglia has not been characterized. In this study we provide a detailed description of a voltage-dependent, inwardly rectifying, cation non-selective current, I h , that was present in around 78% of cultured rat petrosal neurons. Activation of this current appeared to be the basis of the slowly developing depolarizing sag that was recorded under current clamp during application of hyperpolarizing current pulses. Under voltage clamp, I h was activated at voltages negative to -60 mV and had an estimated reversal potential (E h ) of about -33.1±3.4 mV (n=20). Raising extracellular [ K + ] o caused a progressive increase in I h and a positive shift in E h , whereas reducing extracellular [Na + ] o caused a small reduction in I h and an opposite shift in E h . Reducing extracellular [Cl - ] o had no significant effect on E h , though the amplitude of I h decreased. Tail current analysis revealed that the activation curve for I h was well fitted by the Boltzmann distribution, with V 1/2 =-90.6±2.2 mV (mean ± SEM; n=17) and slope factor k=10.8±0.5. I h activated more rapidly at larger hyperpolarizations; elevated [ K + ] o or lowered [Na + ] o increased the time constant (τ) of I h activation. The time constant of deactivation of I h at -60 mV was 317.1±31.9 ms (n=7). Extracellular cesium (10 mM) almost completely blocked I h , whereas barium suppressed I h by around 50%, at a similar concentration. These results, combined with the known sensitivity of the hypoxic afferent discharge to extracellular cesium, suggest that I h likely plays an important physiological role during carotid body chemosensory signaling.