Perturbations of Telmisartan Alone and in Combination with Ranolazineor Dapagliflozin on the Amplitude and Gating of Voltage-gated Na+ Current in Neuroblastoma Neuronal Cells

Abstract

A recent study investigated the correlation between telmisartan (TEL) exposure and Alzheimer’s disease (AD) risk among African Americans (AAs) and European Americans. Their findings indicated that moderate-to-high TEL exposure was linked to a decreased incidence of AD among AAs. These results suggest a potential association between TEL and a reduced risk of AD specifically within the AA population. Here, we investigated the effects of TEL, either alone or in combination with ranolazine (Ran) or dapagliflozin (Dapa), on voltage-gated Na+ currents (I Na) in Neuro-2a cells. TEL, primarily used for treating hypertension and cardiovascular disorders, showed a stimulatory effect on I Na, while Ran and Dapa reversed this stimulation. In Neuro-2a cells, we demonstrated that with exposure to TEL, the transient (I Na(T)) and late (I Na(L)) components of I Na were differentially stimulated with effective EC50’s of 16.9 and 3.1 μM, respectively. The research implies that TEL’s impact on I Na might be associated with enhanced neuronal excitability. This study highlights the complex interplay between TEL, Ran, and Dapa on I Na and their potential implications for AD, emphasizing the need for further investigation to understand the mechanisms involved.