| First Author | Bonin RP | Year | 2013 |
| Journal | PLoS One | Volume | 8 |
| Issue | 3 | Pages | e58679 |
| PubMed ID | 23516534 | Mgi Jnum | J:200188 |
| Mgi Id | MGI:5507770 | Doi | 10.1371/journal.pone.0058679 |
| Citation | Bonin RP, et al. (2013) Hyperpolarization-activated current (In) is reduced in hippocampal neurons from Gabra5-/- mice. PLoS One 8(3):e58679 |
| abstractText | Changes in the expression of gamma-aminobutyric acid type A (GABAA) receptors can either drive or mediate homeostatic alterations in neuronal excitability. A homeostatic relationship between alpha5 subunit-containing GABAA (alpha5GABAA) receptors that generate a tonic inhibitory conductance, and HCN channels that generate a hyperpolarization-activated cation current (Ih) was recently described for cortical neurons, where a reduction in Ih was accompanied by a reciprocal increase in the expression of alpha5GABAA receptors resulting in the preservation of dendritosomatic synaptic function. Here, we report that in mice that lack the alpha5 subunit gene (Gabra5-/-), cultured embryonic hippocampal pyramidal neurons and ex vivo CA1 hippocampal neurons unexpectedly exhibited a decrease in Ih current density (by 40% and 28%, respectively), compared with neurons from wild-type (WT) mice. The resting membrane potential and membrane hyperpolarization induced by blockade of Ih with ZD-7288 were similar in cultured WT and Gabra5-/- neurons. In contrast, membrane hyperpolarization measured after a train of action potentials was lower in Gabra5-/- neurons than in WT neurons. Also, membrane impedance measured in response to low frequency stimulation was greater in cultured Gabra5-/- neurons. Finally, the expression of HCN1 protein that generates Ih was reduced by 41% in the hippocampus of Gabra5-/- mice. These data indicate that loss of a tonic GABAergic inhibitory conductance was followed by a compensatory reduction in Ih. The results further suggest that the maintenance of resting membrane potential is preferentially maintained in mature and immature hippocampal neurons through the homeostatic co-regulation of structurally and biophysically distinct cation and anion channels. |
