Evidence for redox sensing by a human cardiac calcium channel

Padmapriya Muralidharan, Henrietta Cserne Szappanos, Evan Ingley, Livia Hool

Research output: Contribution to journalArticle

12 Citations (Scopus)

Abstract

Ion channels are critical to life and respond rapidly to stimuli to evoke physiological responses. Calcium influx into heart muscle occurs through the ion conducting α1C subunit (Cav1.2) of the L-type Ca2+ channel. Glutathionylation of Cav1.2 results in increased calcium influx and is evident in ischemic human heart. However controversy exists as to whether direct modification of Cav1.2 is responsible for altered function. We directly assessed the function of purified human Cav1.2 in proteoliposomes. Truncation of the C terminus and mutation of cysteines in the N terminal region and cytoplasmic loop III-IV linker did not alter the effects of thiol modifying agents on open probability of the channel. However mutation of cysteines in cytoplasmic loop I-II linker altered open probability and protein folding assessed by thermal shift assay. We find that C543 confers sensitivity of Cav1.2 to oxidative stress and is sufficient to modify channel function and posttranslational folding. Our data provide direct evidence for the calcium channel as a redox sensor that facilitates rapid physiological responses.

Original languageEnglish (US)
Article number19067
JournalScientific Reports
Volume6
DOIs
StatePublished - Jan 11 2016

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Calcium Channels
Oxidation-Reduction
Cysteine
Calcium
Mutation
Protein Folding
Ion Channels
Sulfhydryl Compounds
Myocardium
Oxidative Stress
Hot Temperature
Ions
proteoliposomes

All Science Journal Classification (ASJC) codes

  • General

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Evidence for redox sensing by a human cardiac calcium channel. / Muralidharan, Padmapriya; Cserne Szappanos, Henrietta; Ingley, Evan; Hool, Livia.

In: Scientific Reports, Vol. 6, 19067, 11.01.2016.

Research output: Contribution to journalArticle

Muralidharan, Padmapriya ; Cserne Szappanos, Henrietta ; Ingley, Evan ; Hool, Livia. / Evidence for redox sensing by a human cardiac calcium channel. In: Scientific Reports. 2016 ; Vol. 6.
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