BLUNTED NODOSE GANGLION MECHANOSENSORY AND CHEMOSENSORY SIGNALING POST MYOCARDIAL INFARCTION: INSIGHTS FROM EX VIVO CALCIUM IMAGING

Impairment of baroreflex function predicts poor prognosis in chronic heart failure. Desensitization is attributed to reduced baroreceptor afferent sensitivity in nodose ganglion neurons and peripheral terminals, yet mechanisms remain unclear. We performed ex vivo calcium imaging in male Pirt-Cre;GCaMP6 and TRPV1-Cre;GCaMP6 mice 4 weeks after myocardial infarction (MI; coronary artery ligation) or sham surgery. Isolated nodose ganglia were perfused with nicotine (100 µM) or hypo-osmotic ACSF (5 mM Na⁺) to induce swelling/stretch. We quantified peak amplitude (ΔF/F0), area under the curve (AUC), and calcium entry rate (CER). Data were collected from 4–7 animals, 8–10 ganglia, with ~150–400 neurons/group. In Pirt⁺ neurons, MI strongly blunted nicotine signaling. Peak ΔF/F0 was 38% lower (1.067 to 0.666), AUC was 53% lower (147.5 to 69.1), and CER was 24% lower (0.00780 to 0.00592) (p<0.0001). TRPV1+ nicotine responses were significantly but less reduced after MI, with a peak ΔF/F0 20% lower (1.361 to 1.085), AUC 30% lower (202.4 to 140.8), and CER 12% lower (0.01417 to 0.01247) (p ≤0.0001). After MI, hypo-osmotic responses showed the largest deficit in TRPV1⁺ neurons. Peak ΔF/F0 was 44% lower (1.325 to 0.743), AUC was 51% lower (225.4 to 110.6), and CER was 46% lower (0.00877 to 0.00470) (p<0.0001). In Pirt⁺ neurons, peak ΔF/F0 was 19% lower (0.968 to 0.788), and AUC was 27% lower (154.8 to 113.1) (p<0.0001), while CER was unchanged. These data show that MI remodels nodose signaling in a stimulus- and subtype-dependent manner, potentially contributing to reduced vagal afferent drive and baroreflex dysfunction.