Hyperpolarization‐activated cyclic nucleotide‐gated channels mediate blunted excitability of aortic baroreceptor neurons in diabetic rats

Abstract

Although dysfunction of arterial baroreflex occurs in diabetic humans and animal models of type‐1 diabetes (T1D), the mechanisms involved in the impairment of the baroreflex still remain unclear. The nodose ganglia (NG) contain the cell bodies of the aortic baroreceptor (AB) neurons. Hyperpolarization‐activated cyclic nucleotide‐gated (HCN) channels are expressed in AB neurons and play an important role in regulating the excitability of these sensory neurons. We focused on the AB neurons in the NG to investigate whether the excitability of AB neurons is depressed and whether HCN channels are involved in this depression in streptozotocin (STZ)‐induced T1D rats, using the whole‐cell patch clamp technique. AB neuron excitability (action potential frequency) in the T1D rats was lower than that in the control rats (0.4 ± 0.6 vs 4.6 ± 0.7 spikes/sec, p<0.05; AB neurons were identified by DiI staining). In addition, HCN current density in AB neurons from the T1D rats was bigger than that from the control rats. Furthermore, HCN channel blockers (5 mM cesium chloride and 100 μM ZD‐7288) significantly reduced HCN currents and increased action potential frequency of the AB neurons in control and T1D rats. Using immunofluorescent and western blot analyses, we also found that the expression of HCN1 channel protein in the NG from the T1D rats was higher than that from the control rats. These results indicate that the HCN channels influence the excitability of AB neurons, and more importantly, contribute to the decreased excitability of AB neurons in T1D rats.