Postnatal development of the hyperpolarization-activated excitatory current Ih in XXXX hippocampal pyramidal neurons.

@entity19 @entity5796 @entity43833 @entity4779 @entity377 @entity14819 @entity4778 @entity71009 @entity13786 @entity43831
The hyperpolarization-activated excitatory current I(h) shapes rhythmic firing and other components of excitability in differentiating neurons, and may thus influence activity-dependent CNS development. We therefore studied developmental changes in I(h) and underlying hyperpolarization-activated cyclic @entity377 -gated (HCN) channel subunits in pyramidal neurons of neonatal @entity19 hippocampus using electrophysiological and immunofluorescence approaches. I(h) conductance (at -80 mV) tripled in @entity4779 neurons and quintupled in @entity4778 neurons between postnatal day 1 (P1) and @entity5796 ; parallel changes in membrane area resulted in current density maxima at P5 in @entity4779 and @entity14819 in @entity4778 . Concurrently, I(h) activation times fell sevenfold in @entity4779 and 10-fold in @entity4778 . A computational model indicates that a decrease in I(h) activation time will increase the rhythmic firing rate. Two mechanisms contributed to more rapid I(h) activation at @entity5796 in @entity4779 and @entity4778 neurons: a fall in the intrinsic time constants of two kinetic components, tau(fast) and tau(slow), to 35-40% (at -90 mV) of their P1 values, and a preferential increase in fast component amplitude and contribution to I(h) (from approximately 35% to approximately 74% of total). @entity43831 , @entity43833 , and @entity13786 immunoreactivities showed independent temporal and spatial developmental patterns. @entity43831 immunoreactivity was low at @entity71009 and increased by @entity5796 . @entity43833 immunoreactivity was detected at P1 and increased steadily up to @entity5796 . @entity13786 immunoreactivity was initially low and showed a small increase by @entity5796 . We suggest that developmental increases in I(h) amplitude and activation rate reflect changes in the number and underlying structure of I(h) channels, and that I(h) maturation may shape rhythmic activity important for hippocampal circuit maturation.
