Angiotensin II increases protein expression of hyperpolarization‐activated channels in rat nodose ganglion neurons

Diabetes induces the elevation of endogenous angiotensin II (Ang II), the protein overexpression of hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels, and the increase of HCN currents in the nodose ganglion (NG) neurons. Our previous study showed that Ang II acutely enhanced HCN currents in the NG neurons via NADPH‐superoxide signaling. Therefore, the present study was to measure the effect of Ang II on the protein expression of the HCN channels in the primary nodose neurons isolated from rats. Using immunofluorescent staining, we found that HCN1 was expressed in the A‐type NG neurons, and HCN2 was expressed in the C‐type NG neurons. After NG neurons were treated by Ang II (100 nM, 12 h), HCN2 was also expressed besides overexpression of HCN1 in A‐type NG neurons; and HCN2 was overexpressed in C‐type NG neurons. Whole cell patch clamp data further confirmed that chronic treatment of Ang II (100 nM, 12 h) significantly enhanced the density of the HCN currents in A‐ and C‐type NG neurons. Losartan (an AT 1 receptor antagonist, 1 μM) markedly inhibited the effect of Ang II on the density of the HCN channels. These results indicate that Ang II not only acutely modulates the electrophysiological kinetics of HCN channels, but also chronically induces the protein overexpression of HCN channels.