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Significance TRPML1 (transient receptor potential mucolipin 1) is a Ca2+ -permeable, nonselective cation channel that is localized to late endosomes and lysosomes. Here, we investigated the function of TRPML1 channels in regulating lower urinary tract (LUT) smooth muscle cell (SMC) contractility. We found that TRPML1 forms a stable signaling complex with ryanodine receptors (RyRs) in the sarcoplasmic reticulum (SR). We further showed that TRPML1 channels are important for initiating an essential Ca2+ -signaling negative feedback mechanism between RyRs on SR membranes and K+ channels on the plasma membrane. Knockout of TRPML1 channels in mice impaired this pathway, resulting in LUT smooth muscle hypercontractility and symptoms of overactive bladder. Our findings demonstrate a critical role for TRPML1 in LUT function.

The intracellular Ca 2+ release channel TRPML1 regulates lower urinary tract smooth muscle contractility

The intracellular Ca ²⁺ release channel TRPML1 regulates lower urinary tract smooth muscle contractility