Heterogeneous voltage dependence of inward rectifier currents in spiral ganglion neurons

Inward rectification was characterized in neonatal spiral ganglion neurons maintained in tissue culture. Whole cell current and voltage-clamp techniques were used to show that the hyperpolarization-activated cationic (I(h)) current underlies most or all of the inward rectification demonstrated in these neurons. The average reversal potential (-41.3 mV) and cesium sensitivity were typical of that found in other neurons and cell types. What was unique about the hyperpolarization-activated currents, however, was that the half-maximal voltages (V( 1/4 )) and slope factors (k) that characterized I(h) current activation were graded from neuron to neuron. Voltage-clamp recordings made with standard bath and pipette solutions revealed V( 1/4 ) values that ranged from -78.1 to -122.1 mV, with slope factors from 7.6 to 13.1. These gradations in the voltage-dependent features of the I(h) current did not result from variability in the recording conditions because independently measured Na⁺ current-to-voltage relationships were found to be uniform (peak current at -20 mV). Moreover, the range and average V(1/2) and slope values could be altered with activators [8-(4-chlorophenylthio) adenosine 3',5'-cyclic monophosphate in combination with okadaic acid] or inhibitors {N-[2-(p-bromocinnamylamino)ethyl]-5-isoquinolinesulfonamide} of protein indicating that I(h) current heterogeneity most likely resulted from differential phosphorylation.