Postnatal maturation of the hyperpolarization-activated cation current, Ih, in trigeminal sensory neurons

Cho HJ, Furness JB, Jennings EA. Postnatal maturation of the hyperpolarization-activated cation current, I-h, in trigeminal sensory neurons. J Neurophysiol 106: 2045-2056, 2011. First published July 13, 2011; doi:10.1152/jn.00798.2010.-Hyperpolarization-activated inward currents (I-h) contribute to neuronal excitability in sensory neurons. Four subtypes of hyperpolarization-activated cyclic nucleotide-gated (HCN) channels generate I-h, with different activation kinetics and cAMP sensitivities. The aim of the present study was to examine the postnatal development of I-h and HCN channel subunits in trigeminal ganglion (TG) neurons. I-h was investigated in acutely dissociated TG neurons from rats aged between postnatal day (P) 1 and P35 with whole cell patch-clamp electrophysiology. In voltage-clamp studies, I-h was activated by a series of hyperpolarizing voltage steps from -40 mV to -120 mV in -10-mV increments. Tail currents from a common voltage step (-100 mV) were used to determine I-h voltage dependence. I-h activation was faster in older rats and occurred at more depolarized potentials; the half-maximal activation voltage (V-1/2) changed from -89.4 mV (P1) to -81.6 mV (P35). In current-clamp studies, blocking I-h with ZD7288 caused membrane hyperpolarization and increases in action potential half-duration at all postnatal ages examined. ZD7288 also reduced the action potential firing frequency in multiple-firing neurons. Western blot analysis of the TG detected immunoreactive bands corresponding to all HCN subtypes. HCN1 and HCN2 band density increased with postnatal age, whereas the low-intensity HCN3 and moderate-intensity HCN4 bands were not changed. This study suggests that functional I-h are activated in rat trigeminal sensory neurons from P1 during postnatal development, have an increasing role with age, and modify neuronal excitability.