Hyperpolarization-activated currents regulate excitability in stellate cells of the mammalian ventral cochlear...

The differing biophysical properties of neurons the axons of which form the different pathways from the ventral cochlear nucleus (VCN) determine what acoustic information they can convey. T stellate cells, excitatory neurons the axons of which project locally and to the inferior colliculus, and D stellate cells, inhibitory neurons the axons of which project to the ipsi- and contralateral cochlear nuclei, fire tonically when they are depolarized, and, unlike other cell types in the VCN, their firing rates are sensitive to small changes in resting currents. In both types of neurons, the hyperpolarization-activated current (I(h)) reversed at -40 mV, was activated at voltages negative to -60 mV, and half-activated at approximately -88 mV; maximum hyperpolarization-activated conductances (g(h max)) were 19.1 +/- 2.3 nS in T and 30.3 +/- 2.6 nS in D stellate cells (means +/- SE). Activation and deactivation were slower in T than in D stellate cells. In both types of stellate cells, 50 microM 4(N-ethyl-N-phenylamino)1,2-dimethyl-6-(methylamino) pyridinium chloride (ZD7288) and 2 mM Cs(+) blocked a 6- to 10-fold greater conductance than the voltage-dependent g(h) determined from Boltzmann analyses at -62 mV. The voltage-insensitive, ZD7288-sensitive conductance was proportional to g(h max) and g(input). 8-Br-cAMP shifted the voltage dependence of I(h) in the depolarizing direction, increased the rate of activation, and slowed its deactivation in both T and D stellate cells. Reduction in temperature did not change the voltage dependence but reduced the maximal g(h) with a Q(10) of 1.3 and slowed the kinetics with a Q(10) of 3.3.