Investigation on Transient Receptor Potential Vanilloid 1 (TRPv1) Activation in Skeletal Muscle: Pilot Studies

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Transient Receptor Potential Vanilloid 1 (TRPv1) is a Ca2+ ion channel predominately studied in neuronal cells and has been found to have sex-differential expression in mouse arterial smooth muscle. More recently, TRPv1 expression has also been observed in skeletal muscle. Among other stimuli, osmotic stress has shown to activate TRPv1 in different tissues (e.g., retinal ganglion and supraoptic nuclear cells). However, the effect of hyperglycemia- and dehydration-induced osmotic stress and the sex-differential expression on TRPv1 in skeletal muscle is not known. PURPOSES: To examine the effect of sex ( Pilot 1), hyperglycemia ( Pilot 2), and dehydration ( Pilot 3) on TRPv1 in skeletal muscle. HYPOTHESES: We hypothesized that TRPv1 would be different between sexes ( Pilot 1), would be higher in hyperglycemic rats compared to healthy controls ( Pilot 2), and would be greater in dehydrated than hydrated state in men ( Pilot 3). METHODS: To accomplish these purposes, we analyzed a subset of samples from three previously completed projects. Pilot 1: Vastus lateralis (VL) muscles were collected from untrained men ( n=3) and women ( n=3) at baseline. Pilot 2: Rats fed a high fat diet and injected with streptozotocin (35 mg/kg) (HFD; n=3; non-fasting blood glucose (NFBG) ≥300mg/dL) were compared to rats fed a normal diet (CON; n=3; NFBG <300mg/dL). Soleus (Sol) muscle was collected after 7 weeks of feeding. Pilot 3: Lastly, VL muscles were collected from trained men (n=5) either dehydrated (DEHY; 296 ± 6 plasma mmol/kg) or hydrated (EUHY; 283 ± 5 plasma mmol/kg) for 24 hours. Rat Sol and human VL samples were analyzed for TRPv1 and p-TRPv1ser502 protein content. TRPv1 activation was calculated as p-TRPv1ser502/ TRPv1/ total protein. Student’s T-tests and effect sizes (ES; small [≤0.49], medium [0.5-0.79], or large [≥0.8] effect) were used to detect differences. Results: Pilot 1: A significant ( p<0.05) difference was observed for TRPv1 with greater expression in men than women (43%, p=0.03, d=2.757). A medium ES was observed for TRPv1 activation (31%, p=0.42, d=0.728) being greater in men compared to women. Pilot 2: No significant difference was observed for TRPv1 and TRPv1 activation between CON and HFD rats. A medium ES was observed for TRPv1 expression (-9%, p=0.31, d=0.441) being lower in HFD compared to CON. A large effect size was observed for TRPv1 activation (30%, p=0.18, d=1.689) being greater in HFD compared to CON. Pilot 3: No significant difference was observed for TRPv1 and TRPv1 activation between EUHY and DEHY. A large ES was observed for TRPv1 (34%, p=0.15, d=0.995) and small ES was observed for TRPv1 activation (2%, p=0.80, d=0.164) being greater in DEHY compared to EUHY. CONCLUSION: These data are the first to illustrate the potential difference in TRPv1 in skeletal muscle. Future research is needed to explore the impact of differential TPRv1 activation on downstream Ca2+ signaling between sexes, dehydration, and hyperglycemic models. This is the full abstract presented at the American Physiology Summit 2024 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.