Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels

S M Raquibul Hasan, Alasdair T.S. Leeson-Payne, Jonathan Jaggar, Xuming Zhang

Research output: Contribution to journalArticle

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Abstract

TRPA1 is a Ca 2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca 2+, with low Ca 2+ potentiating and high Ca 2+ inactivating TRPA1. However, it remains unknown how Ca 2+ exerts such contrasting effects. Here, we show that Ca 2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca 2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca 2+-evoked potentiation of TRPA1 at low Ca 2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca 2+. Ca 2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca 2+ sensor enabling TRPA1 to respond to diverse Ca 2+ signals distinctly.

Original languageEnglish (US)
Article number45098
JournalScientific reports
Volume7
DOIs
StatePublished - Mar 23 2017

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Calmodulin
Sensation Disorders
Ion Channels
Pain

All Science Journal Classification (ASJC) codes

  • General

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Calmodulin is responsible for Ca2+-dependent regulation of TRPA1 Channels. / Hasan, S M Raquibul; Leeson-Payne, Alasdair T.S.; Jaggar, Jonathan; Zhang, Xuming.

In: Scientific reports, Vol. 7, 45098, 23.03.2017.

Research output: Contribution to journalArticle

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abstract = "TRPA1 is a Ca 2+-permeable ion channel involved in many sensory disorders such as pain, itch and neuropathy. Notably, the function of TRPA1 depends on Ca 2+, with low Ca 2+ potentiating and high Ca 2+ inactivating TRPA1. However, it remains unknown how Ca 2+ exerts such contrasting effects. Here, we show that Ca 2+ regulates TRPA1 through calmodulin, which binds to TRPA1 in a Ca 2+-dependent manner. Calmodulin binding enhanced TRPA1 sensitivity and Ca 2+-evoked potentiation of TRPA1 at low Ca 2+, but inhibited TRPA1 sensitivity and promoted TRPA1 desensitization at high Ca 2+. Ca 2+-dependent potentiation and inactivation of TRPA1 were selectively prevented by disrupting the interaction of the carboxy-lobe of calmodulin with a calmodulin-binding domain in the C-terminus of TRPA1. Calmodulin is thus a critical Ca 2+ sensor enabling TRPA1 to respond to diverse Ca 2+ signals distinctly.",
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