Remodeling of hyperpolarization-activated current, Ih, in Ah-type visceral ganglion neurons following ovariectomy in adult rats.
Hyperpolarization-activated currents (Ih) mediated by hyperpolarization-activated cyclic nucleotide-gated (HCN) channels modulate excitability of myelinated A- and Ah-type visceral ganglion neurons (VGN). Whether alterations in Ih underlie the previously reported reduction of excitability of myelinated Ah-type VGNs following ovariectomy (OVX) has remained unclear. Here we used the intact nodose ganglion preparation in conjunction with electrophysiological approaches to examine the role of Ih remodeling in altering Ah-type neuron excitability following ovariectomy in adult rats. Ah-type neurons were identified based on their afferent conduction velocity. Ah-type neurons in nodose ganglia from non-OVX rats exhibited a voltage 'sag' as well as 'rebound' action potentials immediately following hyperpolarizing current injections, which both were suppressed by the Ih blocker ZD7288. Repetitive spike activity induced afterhyperpolarizations lasting several hundreds of milliseconds (termed post-excitatory membrane hyperpolarizations, PEMHs), which were significantly reduced by ZD7288, suggesting that they resulted from transient deactivation of Ih during the preceding spike trains. Ovariectomy reduced whole-cell Ih density, caused a hyperpolarizing shift of the voltage-dependence of Ih activation, and slowed Ih activation. OVX-induced Ih remodeling was accompanied by a flattening of the stimulus frequency/response curve and loss of PEMHs. Also, HCN1 mRNA levels were reduced by ∼30% in nodose ganglia from OVX rats compared with their non-OVX counterparts. Acute exposure of nodose ganglia to 17beta-estradiol partly restored Ih density and accelerated Ih activation in Ah-type cells. In conclusion, Ih plays a significant role in modulating the excitability of myelinated Ah-type VGNs in adult female rats.
State Key Laboratory of Robotics and System, Harbin Institute of Technology, Harbin, Heilongjiang, China.
Guo-Fen
GF
Qiao
Zhao
Z
Qian
Hong-Li
HL
Sun
Wen-Xiao
WX
Xu
Zhen-Yu
ZY
Yan
Yang
Y
Liu
Jia-Ying
JY
Zhou
Hao-Cheng
HC
Zhang
Li-Juan
LJ
Wang
Xiao-Dong
XD
Pan
Yili
Y
Fu
D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000378:metabolism*; D004958:Estradiol / Q000494:pharmacology; D005071:Evoked Potentials / Q000187:drug effects / Q000502:physiology; D005260:Female; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology*; D009186:Myelin Sheath / Q000378:metabolism; D009620:Nodose Ganglion / Q000187:drug effects / Q000502:physiology*; D010052:Ovariectomy; D018408:Patch-Clamp Techniques; D020671:Posterior Horn Cells / Q000187:drug effects / Q000502:physiology*; D051381:Rats; D014630:Vagus Nerve / Q000187:drug effects / Q000502:physiology
D054815:Cyclic Nucleotide-Gated Cation Channels; D004958:Estradiol