Kv7 channel dysfunction is involved in hyperactivity of posterior insular cortex neurons in hypertension

Elevated sympathetic outflow is a key component of pathogenesis of hypertension. However, the source driving increased sympathetic vasomotor tone remain unclear. The posterior insular cortex (PIC) is a brain region involved in regulating blood pressure and sympathetic tone. Neurons in the PIC project to the rostral ventrolateral medulla (RVLM). Neuronal Kv7 channels play a vital role in controlling the excitability of neurons. This study determined the role of Kv7 channels in regulating RVLM-projecting PIC neurons in spontaneously hypertensive rats (SHRs). Kv7.2, Kv7.3, and Kv7.5 subunits expression level were compared between Wistar-Kyoto (WKY) rats and SHRs. Whole-cell recording was used to compare the firing activity and M-current in RVLM-projecting PIC neurons retrogradely labelled by Fluospheres injected into the RVLM. We found that the protein expression levels of Kv7.3 and Kv7.5 in the PIC were significantly lower in SHRs than in WKY rats, while Kv7.2 levels did not differ between WKY and SHRs. Immunofluorescent staining reviewed that Kv7.2, Kv7.3, and Kv7.5 subunits were expressed on retrogradely labeled RVLM-projecting PIC neurons. Electrophysiological recording results showed that the basal firing activity of labeled PIC-RVLM projection neurons was significantly greater in SHRs than in WKY rats. Blocking M-currents with XE-991 increased both spontaneous and depolarization-triggered firing rate of RVLM projecting PIC neurons in WKY rats, whereas XE-991 did not alter either spontaneous or depolarization-triggered firing rate of these neurons in SHRs. These data suggest that hyperactivity of RVLM projecting PIC neurons in SHRs is attributed to reduction of Kv7 channel expression and activity. Our findings revealed a novel mechanism underlying elevated sympathetic vasomotor activity in hypertension. National Heart, Lung, and Blood Institute grant HL142133 and HL139523, and HL159157 to D-P. L. This is the full abstract presented at the American Physiology Summit 2023 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.