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钙诱导钙释放接近毛细胞 BK 通道通过 PKA 激活揭示。

Calcium-induced calcium release in proximity to hair cell BK channels revealed by PKA activation.

机构信息

Department of Neurology, Yale School of Medicine, New Haven, CT, USA.

Department of Otolaryngology-Head and Neck Surgery, Shanghai Ninth People's Hospital, Shanghai Jiaotong University School of Medicine, Shanghai, China.

出版信息

Physiol Rep. 2020 Aug;8(15):e14449. doi: 10.14814/phy2.14449.

DOI:10.14814/phy2.14449
PMID:32748549
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7399380/
Abstract

Large-conductance calcium-activated potassium (BK) channels play a critical role in electrical resonance, a mechanism of frequency selectivity in chicken hair cells. We determine that BK currents are dependent on inward flow of Ca , and intracellular buffering of Ca . Entry of Ca is further amplified locally by calcium-induced Ca release (CICR) in close proximity to plasma membrane BK channels. Ca imaging reveals peripheral clusters of high concentrations of Ca that are suprathreshold to that needed to activate BK channels. Protein kinase A (PKA) activation increases the size of BK currents likely by recruiting more BK channels due to spatial spread of high Ca concentrations in turn from increasing CICR. STORM imaging confirms the presence of nanodomains with ryanodine and IP3 receptors in close proximity to the Slo subunit of BK channels. Together, these data require a rethinking of how electrical resonance is brought about and suggest effects of CICR in synaptic release. Both genders were included in this study.

摘要

大电导钙激活钾 (BK) 通道在电共振中发挥着关键作用，电共振是鸡毛细胞频率选择性的一种机制。我们确定 BK 电流依赖于 Ca 的内流和 Ca 的细胞内缓冲。Ca 的进入进一步通过紧邻质膜 BK 通道的钙诱导钙释放 (CICR) 进行局部放大。钙成像揭示了外周存在高浓度 Ca 的簇，这些 Ca 的浓度超过了激活 BK 通道所需的阈值。蛋白激酶 A (PKA) 的激活增加了 BK 电流的大小，这可能是由于 Ca 浓度的空间扩散增加了 CICR，从而募集了更多的 BK 通道。STORM 成像证实了在靠近 BK 通道的 Slo 亚基的位置存在与 Ryanodine 和 IP3 受体紧密接近的纳米域。这些数据共同要求重新思考电共振是如何产生的，并提示 CICR 在突触释放中的作用。这项研究包括了男性和女性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/994393c644a9/PHY2-8-e14449-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/72e9f7525a46/PHY2-8-e14449-g001.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/72608dbe7e31/PHY2-8-e14449-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/5a994985af58/PHY2-8-e14449-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/033ed7bfea9e/PHY2-8-e14449-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/7e45f6d65be0/PHY2-8-e14449-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/a16bdd70f10b/PHY2-8-e14449-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/90313fa90163/PHY2-8-e14449-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/659512daefab/PHY2-8-e14449-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/994393c644a9/PHY2-8-e14449-g011.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/72e9f7525a46/PHY2-8-e14449-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/c07052ba6063/PHY2-8-e14449-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/ed6e05c465d0/PHY2-8-e14449-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/72608dbe7e31/PHY2-8-e14449-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/5a994985af58/PHY2-8-e14449-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/033ed7bfea9e/PHY2-8-e14449-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/7e45f6d65be0/PHY2-8-e14449-g007.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/a16bdd70f10b/PHY2-8-e14449-g008.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/90313fa90163/PHY2-8-e14449-g009.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/659512daefab/PHY2-8-e14449-g010.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb65/7399380/994393c644a9/PHY2-8-e14449-g011.jpg

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