Igniting Ca 2+ sparks with TRPML1
| العنوان: | Igniting Ca 2+ sparks with TRPML1 |
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| المؤلفون: | Gerard P. Sergeant, Keith D. Thornbury, Mark A. Hollywood |
| المصدر: | Proceedings of the National Academy of Sciences. 117:32836-32838 |
| بيانات النشر: | Proceedings of the National Academy of Sciences, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, BK channel, Multidisciplinary, biology, Depolarization, Iberiotoxin, urologic and male genital diseases, medicine.disease, female genital diseases and pregnancy complications, 03 medical and health sciences, Transient receptor potential channel, chemistry.chemical_compound, 030104 developmental biology, 0302 clinical medicine, Urethra, medicine.anatomical_structure, chemistry, Overactive bladder, biology.protein, Biophysics, medicine, Myocyte, Paxilline, 030217 neurology & neurosurgery |
| الوصف: | Storage and voiding of urine in mammals is accomplished by a reciprocal contractile relationship between the bladder and the urethra. During the storage phase, the urethra remains contracted to prevent leakage of urine, while the bladder is relaxed to accommodate the increased volume of urine. Conversely, during voiding, the urethra relaxes, while the bladder contracts to generate an intravesical pressure which exceeds that in the urethra (1). The cellular mechanisms that govern these functions are only partly understood, and there is a particular paucity of data on the cellular processes that underlie tonic contraction of urethral smooth muscle (USM). This issue is addressed in PNAS by Griffin et al. (2), who demonstrate a critical role for transient receptor potential mucolipin 1 (TRPML1) channels in the regulation of detrusor and USM excitability. Spontaneous phasic contractions of the detrusor are directly correlated with bursts of action potentials, mediated by activation of voltage-dependent CaV1.2 channels (VDCC) (3). Selective blockade of large conductance Ca2+-activated K+ (BK) channels with iberiotoxin or paxilline induced depolarization and increased the amplitude and duration of spontaneous action potentials and phasic contractions (4). Furthermore, transgenic mice that lack the BK channel α subunit demonstrate a marked increase in urination frequency, corresponding to an overactive bladder (OAB) phenotype (5). This is thought to result from increased Ca2+ influx via VDCC as a result of diminished negative feedback, which limits Ca2+ entry. The BK channel blocker, penitrem A, increased the amplitude and duration of action potentials in USM cells (USMC) (6, 7), indicating that BK channels are also important regulators of USM excitability. The primary activation mechanism for BK channels in detrusor myocytes is localized Ca2+ release from intracellular stores, referred to as Ca2+ sparks (8). The resultant BK currents are termed … [↵][1]1To whom correspondence may be addressed. Email: gerard.sergeant{at}dkit.ie. [1]: #xref-corresp-1-1 |
| تدمد: | 1091-6490 0027-8424 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_________::13b6472eb3410ed5f102474574c0bd78Test https://doi.org/10.1073/pnas.2022896117Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi...........13b6472eb3410ed5f102474574c0bd78 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 10916490 00278424 |
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