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• W2080688001 abstract "Properties, developmental regulation, and cAMP modulation of the hyperpolarization-activated current ( I h ) were investigated by the whole cell patch-clamp technique in vestibular ganglion neurons of the rat at two postnatal stages (P7–10 and P25–28). In addition, by RT-PCR and immunohistochemistry the identity and distribution of hyperpolarization-activated and cyclic nucleotide-gated channel (HCN) isoforms that generate I h were investigated. I h current density was larger in P25–28 than P7–10 rats, increasing 410% for small cells (<30 pF) and 200% for larger cells (>30 pF). The half-maximum activation voltage ( V 1/2 ) of I h was −102 mV in P7–10 rats and in P25–28 rats shifted 7 mV toward positive voltages. At both ages, intracellular cAMP increased I h current density, decreased its activation time constant (τ), and resulted in a rightward shift of V 1/2 by 9 mV. Perfusion of 8-BrcAMP increased I h amplitude and speed up its activation kinetics. I h was blocked by Cs + , zatebradine, and ZD7288. As expected, these drugs also reduced the voltage sag caused with hyperpolarizing pulses and prevented the postpulse action potential generation without changes in the resting potential. RT-PCR analysis showed that HCN1 and HCN2 subunits were predominantly amplified in vestibular ganglia and end organs and HCN3 and HCN4 to a lesser extent. Immunohistochemistry showed that the four HCN subunits were differentially expressed (HCN1 > HCN2 > HCN3 ≥ HCN4) in ganglion slices and in cultured neurons at both P7–10 and P25–28 stages. Developmental changes shifted V 1/2 of I h closer to the resting membrane potential, increasing its functional role. Modulation of I h by cAMP-mediated signaling pathway constitutes a potentially relevant control mechanism for the modulation of afferent neuron discharge." @default.
• W2080688001 created "2016-06-24" @default.
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• W2080688001 date "2012-10-15" @default.
• W2080688001 modified "2023-09-24" @default.
• W2080688001 title "Molecular identity, ontogeny, and cAMP modulation of the hyperpolarization-activated current in vestibular ganglion neurons" @default.
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• W2080688001 doi "https://doi.org/10.1152/jn.00337.2012" @default.
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