Introduction: Highly coordinated relaxation of smooth muscle cells (SMCs) is a requirement for penile erection. Previous studies in the corpus cavernosum (CC) have shown that blocking the Ca2+ activated Cl- channel Ano1 inhibited contractile, electrical and intracellular Ca2+ activity. Penile activity is influenced by neural inputs with SMCs thought to be directly targeted by neurotransmitters due to their expression of soluble guanylate cyclase (sGC), the receptor for nitric oxide (NO). However, as the CC is sparsely innervated, a cellular mediator could be present between nerves and CCSMCs. Despite this, the specific cell type that expresses Ano1 has not been identified, with previous studies relying on morphological identification of SMCs alone. Platelet derived growth factor receptor-a (PDGFRa)+ cells have been identified in other visceral smooth muscles including the gastrointestinal and urinary tracts where they mediate inhibitory neurotransmission. In the renal pelvis, PDGFRa+ cells express Ano1. The aim of this study is to identify and characterize the cell type that expresses Ano1 and to determine whether these cells mediate neurotransmission in the CC. Methods: Cells were isolated from the CC of mice expressing eGFP in PDGFRa+ cells (PDGFRa+-eGFP mice) and SMCs (SmMHC-eGFP mice). Isolated cells were sorted with FACS. Enriched PDGFRa and SMC populations were examined using qPCR for expression of cell specific markers (Pdfgra and smooth muscle myosin heavy chain (Myh11)) to ensure purity. Purified PDGFRa+ cells and SMCs were evaluated with ddPCR to examine the expression of Ano1 and genes encoding signaling proteins from the NO pathway. Results: PDGFRa+ cells isolated with FACS belonged to bright and dim populations. While qPCR revealed that the bright and dim populations expressed similar levels of Pdgfra, the dim population also expressed Myh11. In contrast, SMCs purified using FACS expressed Myh11 and Pdgfra, similar to the dim population of PDGFRa+ cells. ddPCR revealed that both the dim population of PDGFRa+ cells and SMCs expressed Ano1 and genes encoding signaling proteins from the NO pathway. Conclusions: These data suggest that Ano1 is expressed by atypical SMCs that also express PDGFRa. Therefore, these cells are a potential novel target for the treatment of erectile dysfunction. Future directions of this project include investigating the interactions between PDGFRa+ cells, SMCs and neurons. SOURCE OF Funding: Urology Care Foundation Research Scholar Award, sponsored by the Sexual Medicine Society of North America.
