An anatomical basis for interaction between acid‐sensing ion channel 1 and neuronal nitric oxide synthase in rat and human cerebral arteries (853.8)

Abstract

Acid‐sensing ion channel type 1 (ASIC1), which may play contribute to synaptic plasticity, memory, fear conditioning and ischemic brain injury, is found primarily in brain; but it is also expressed in isolated mouse cerebrovascular smooth muscle cells. However, ASIC1 has not been shown in intact cerebral arteries. In contrast, neuronal nitric oxide synthase (nNOS), which is responsible for synthesis of NO, is found in human and animal cerebral arteries where NO may modulate protein activity. In that NO also modulates proton‐gated currents in cultured cells expressing ASIC1, we hypothesized that ASIC1 and nNOS may be expressed in close proximity in cerebral arteries. By Western blot analysis we found that ASIC1 is expressed in cerebral arteries in rat and human. Using confocal microscopy we found that ASIC1‐immunoreactivity (IR) was present in the anterior cerebral artery (ACA), middle cerebral artery (MCA), posterior cerebral artery (PCA) and basilar artery (BA) of rat and human. Colocalization of ASIC1‐IR with IR of alpha‐smooth muscle actin confirmed that ASIC1 was located in the smooth muscle layer of cerebral arteries while nNOS‐IR was found in neighboring endothelial and adventitial layers of the ACA, MCA, PCA and BA in rat and human. The proximity of ASIC1‐IR and nNOS‐IR provides an anatomical basis for possible interactions between ASIC1 and nNOS in regulating vasomotor tone of cerebral arteries.Grant Funding Source: Supported by NIH RO1 HL 088090 and a VA Merit Review