Effect of hypoxia on hyperpolarization-activated current in mouse dorsal root ganglion neurons

The properties of hyperpolarization-activated current (I-h) in mouse dorsal root ganglion (DRG) neurons and the effect of hypoxia on the current have been studied using whole-cell configuration of the patch clamp technique. Under voltage-clamp mode, Ih, blocked by 1 mM extracelluar CsCl, was present in 75.5% of mouse DRG neurons. The distribution rate increased as the neurons become larger, 5.3%, 79.8% and 94.2% in small, medium and large neurons, respectively. Both Ih density and the rate of Ih activation increased in response to more hyperpolarized potential. The activation of Ih current in larger neuron was faster than in smaller neuron, there was a significant correlation between the time constant Of Ih activation and neuron's size. However, Ih density did not show any correlation with neuron's size. Under current-clamp mode,'depolarizing sag'was observed in all neurons with Ih current The reversal potential (V-rev) and the maximal conductance density of I-h (G(h.m -density)) were -31.0 +/- 4.8 mV and 0.17 +/- 0.02 nS/pF, with a half-activated potential (V-0.5 = -99.4 +/- 1.1 mv) and a slope factor (kappa = -10.2 +/- 0.3 mV). There was a correlation between neuron's size and G(h.max-density) only. According to the effect of hypoxia on resting membrane potential, there were hypoxia-sensitive and hypoxia-insensitive neurons. In the hypoxia-sensitive neurons, Ih was fully abolished by hypoxia, although the resting membrane potential was hyperpolarized. V-0.5 and V-rev were shifted about 30 mV toward hyperpolarization, whereas Gh.m -density and K were not affected by hypoxia. We suggest that the kinetics and voltage-dependent characteristics Of I-h are varied in mouse DRG neurons with different size. Hypoxia inhibits Ih in the hypoxia-sensitive neurons by shifting its activation potential to a more hyperpolarized level. (c) 2006 Elsevier B.V. All rights reserved.